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1. The Pluto system: Initial results from its exploration by New Horizons

Author

Stern, S. A., Bagenal, F., Ennico, K., Gladstone, G. R., Grundy, W. M., McKinnon, W. B., Moore, J. M., Olkin, C. B., Spencer, J. R., Weaver, H. A., Young, L. A., Andert, T., Andrews, J., Banks, M., Bauer, B., Bauman, J., Barnouin, O. S., Bedini, P., Beisser, K., Beyer, R. A., Bhaskaran, S., Binzel, R. P., Birath, E., Bird, M., Bogan, D. J., Bowman, A., Bray, V. J., Brozovic, M., Bryan, C., Buckley, M. R., Buie, M. W., Buratti, B. J., Bushman, S. S., Calloway, A., Carcich, B., Cheng, A. F., Conard, S., Conrad, C. A., Cook, J. C., Cruikshank, D. P., Custodio, O. S., Ore, C. M. Dalle, Deboy, C., Dischner, Z. J. B., Dumont, P., Earle, A. M., Elliott, H. A., Ercol, J., Ernst, C. M., Finley, T., Flanigan, S. H., Fountain, G., Freeze, M. J., Greathouse, T., Green, J. L., Guo, Y., Hahn, M., Hamilton, D. P., Hamilton, S. A., Hanley, J., Harch, A., Hart, H. M., Hersman, C. B., Hill, A., Hill, M. E., Hinson, D. P., Holdridge, M. E., Horanyi, M., Howard, A. D., Howett, C. J. A., Jackman, C., Jacobson, R. A., Jennings, D. E., Kammer, J. A., Kang, H. K., Kaufmann, D. E., Kollmann, P., Krimigis, S. M., Kusnierkiewicz, D., Lauer, T. R., Lee, J. E., Lindstrom, K. L., Linscott, I. R., Lisse, C. M., Lunsford, A. W., Mallder, V. A., Martin, N., McComas, D. J., McNutt Jr., R. L., Mehoke, D., Mehoke, T., Melin, E. D., Mutchler, M., Nelson, D., Nimmo, F., Nunez, J. I., Ocampo, A., Owen, W. M., Paetzold, M., Page, B., Parker, A. H., Parker, J. W., Pelletier, F., Peterson, J., Pinkine, N., Piquette, M., Porter, S. B., Protopapa, S., Redfern, J., Reitsema, H. J., Reuter, D. C., Roberts, J. H., Robbins, S. J., Rogers, G., Rose, D., Runyon, K., Retherford, K. D., Ryschkewitsch, M. G., Schenk, P., Schindhelm, R., Sepan, B., Showalter, M. R., Singer, K. N., Soluri, M., Stanbridge, D., Steffl, A. J., Strobel, D. F., Stryk, T., Summers, M. E., Szalay, J. R., Tapley, M., Taylor, A., Taylor, H., Throop, H. B., Tsang, C. C. C., Tyler, G. L., Umurhan, O. M., Verbiscer, A. J., Versteeg, M. H., Vincent, M., Webbert, R., Weidner, S., Weigle II, G. E., White, O. L., Whittenburg, K., Williams, B. G., Williams, K., Williams, S., Woods, W. W., Zangari, A. M., and Zirnstein, E.

Subjects
Astrophysics - Earth and Planetary Astrophysics
Abstract

The Pluto system was recently explored by NASA's New Horizons spacecraft, making closest approach on 14 July 2015. Pluto's surface displays diverse landforms, terrain ages, albedos, colors, and composition gradients. Evidence is found for a water-ice crust, geologically young surface units, surface ice convection, wind streaks, volatile transport, and glacial flow. Pluto's atmosphere is highly extended, with trace hydrocarbons, a global haze layer, and a surface pressure near 10 microbars. Pluto's diverse surface geology and long-term activity raise fundamental questions about how small planets remain active many billions of years after formation. Pluto's large moon Charon displays tectonics and evidence for a heterogeneous crustal composition, its north pole displays puzzling dark terrain. Small satellites Hydra and Nix have higher albedos than expected., Comment: 8 pages - Initial Science paper from NASA's New Horizons Pluto Encounter

Published
2015
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2. De novo truncating variants in the intronless IRF2BPL are responsible for developmental epileptic encephalopathy

Author

Tran Mau-Them, F., Guibaud, L., Duplomb, L., Keren, B., Lindstrom, K., Marey, I., Mochel, F., van den Boogaard, M. J., Oegema, R., Nava, C., Masurel, A., Jouan, T., Jansen, F. E., Au, M., Chen, Agnes H., Cho, M., Duffourd, Y., Lozier, E., Konovalov, F., Sharkov, A., Korostelev, S., Urteaga, B., Dickson, P., Vera, M., Martínez-Agosto, Julián A., Begemann, A., Zweier, M., Schmitt-Mechelke, T., Rauch, A., Philippe, C., van Gassen, K., Nelson, S., Graham, Jr, J. M., Friedman, J., Faivre, L., Lin, H. J., Thauvin-Robinet, C., and Vitobello, A.

Published
2019
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4. Establishing the phenotypic spectrum of ZTTK syndrome by analysis of 52 individuals with variants in SON

Author

Dingemans, A.J.M., Truijen, K.M.G., Kim, J.H., Alaçam, Z., Faivre, L., Collins, K.M., Gerkes, E.H., Haelst, M. van, Laar, I. van de, Lindstrom, K., Nizon, M., Pauling, J., Heropolitańska-Pliszka, E., Plomp, A.S., Racine, C., Sachdev, R., Sinnema, M., Skranes, J., Veenstra-Knol, Hermine E., Verberne, E.A., Vulto-van Silfhout, A.T., Wilsterman, M.E., Ahn, E.E., Vries, B.B.A. de, Vissers, L.E.L.M., Dingemans, A.J.M., Truijen, K.M.G., Kim, J.H., Alaçam, Z., Faivre, L., Collins, K.M., Gerkes, E.H., Haelst, M. van, Laar, I. van de, Lindstrom, K., Nizon, M., Pauling, J., Heropolitańska-Pliszka, E., Plomp, A.S., Racine, C., Sachdev, R., Sinnema, M., Skranes, J., Veenstra-Knol, Hermine E., Verberne, E.A., Vulto-van Silfhout, A.T., Wilsterman, M.E., Ahn, E.E., Vries, B.B.A. de, and Vissers, L.E.L.M.

Abstract

Contains fulltext : 248367.pdf (Publisher’s version ) (Closed access), Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome, an intellectual disability syndrome first described in 2016, is caused by heterozygous loss-of-function variants in SON. Its encoded protein promotes pre-mRNA splicing of many genes essential for development. Whereas individual phenotypic traits have previously been linked to erroneous splicing of SON target genes, the phenotypic spectrum and the pathogenicity of missense variants have not been further evaluated. We present the phenotypic abnormalities in 52 individuals, including 17 individuals who have not been reported before. In total, loss-of-function variants were detected in 49 individuals (de novo in 47, inheritance unknown in 2), and in 3, a missense variant was observed (2 de novo, 1 inheritance unknown). Phenotypic abnormalities, systematically collected and analyzed in Human Phenotype Ontology, were found in all organ systems. Significant inter-individual phenotypic variability was observed, even in individuals with the same recurrent variant (n = 13). SON haploinsufficiency was previously shown to lead to downregulation of downstream genes, contributing to specific phenotypic features. Similar functional analysis for one missense variant, however, suggests a different mechanism than for heterozygous loss-of-function. Although small in numbers and while pathogenicity of these variants is not certain, these data allow for speculation whether de novo missense variants cause ZTTK syndrome via another mechanism, or a separate overlapping syndrome. In conclusion, heterozygous loss-of-function variants in SON define a recognizable syndrome, ZTTK, associated with a broad, severe phenotypic spectrum, characterized by a large inter-individual variability. These observations provide essential information for affected individuals, parents, and healthcare professionals to ensure appropriate clinical management.

Published
2022

6. Nodulation Genes of Rhizobium Galegae

Author

Lindstrom, K., Paulin, L., Roos, C., Suominen, L., Summerfield, R. J., editor, Tikhonovich, Igor A., editor, Provorov, Nikolai A., editor, Romanov, Vassily I., editor, and Newton, William E., editor

Published
1995
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7. PLANETARY SCIENCE: The Pluto system: Initial results from its exploration by New Horizons

Author

Stern, S. A., Bagenal, F., Ennico, K., Gladstone, G. R., Grundy, W. M., McKinnon, W. B., Moore, J. M., Olkin, C. B., Spencer, J. R., Weaver, H. A., Young, L. A., Andert, T., Andrews, J., Banks, M., Bauer, B., Bauman, J., Barnouin, O. S., Bedini, P., Beisser, K., Beyer, R. A., Bhaskaran, S., Binzel, R. P., Birath, E., Bird, M., Bogan, D. J., Bowman, A., Bray, V. J., Brozovic, M., Bryan, C., Buckley, M. R., Buie, M. W., Buratti, B. J., Bushman, S. S., Calloway, A., Carcich, B., Cheng, A. F., Conard, S., Conrad, C. A., Cook, J. C., Cruikshank, D. P., Custodio, O. S., Ore, Dalle C. M., Deboy, C., Dischner, Z. J. B., Dumont, P., Earle, A M., Elliott, H. A, Ercol, J., Ernst, C. M., Finley, T., Flanigan, S. H., Fountain, G., Freeze, M. J., Greathouse, T., Green, J. L., Guo, Y., Hahn, M., Hamilton, D. P., Hamilton, S. A., Hanley, J., Harch, A., Hart, H. M., Hersman, C. B., Hill, A., Hill, M. E., Hinson, D. P., Holdridge, M. E., Horanyi, M., Howard, A. D., Howett, C. J. A., Jackman, C., Jacobson, R. A., Jennings, D. E., Kammer, J. A., Kang, H. K., Kaufmann, D. E., Kollmann, P., Krimigis, S. M., Kusnierkiewicz, D., Lauer, T. R., Lee, J. E., Lindstrom, K. L., Linscott, I. R., Lisse, C. M., Lunsford, A. W., Mallder, V. A., Martin, N., McComas, D. J., McNutt, R. L., Jr., Mehoke, D., Mehoke, T., Melin, E. D., Mutchler, M., Nelson, D., Nimmo, F., Nunez, J. I., Ocampo, A., Owen, W. M., Paetzold, M., Page, B., Parker, A. H., Parker, J. W., Pelletier, F., Peterson, J., Pinkine, N., Piquette, M., Porter, S. B., Protopapa, S., Redfern, J., Reitsema, H. J., Reuter, D. C., Roberts, J. H., Bobbins, S. J., Rogers, G., Rose, D., Runyon, K., Retherford, K. D., Ryschkewitsch, M. G., Schenk, P., Schindhelm, E., Sepan, B., Showalter, M. R., Singer, K. N., Soluri, M., Stanbridge, D., Steffl, A. J., Strobel, D. F., Stryk, T., Summers, M. E., Szalay, J. R., Tapley, M., Taylor, A., Taylor, H., Throop, H. B., Tsang, C. C. C., Tyler, G. L., Umurhan, O. M., Verbiscer, A. J., Versteeg, M. H., Vincent, M., Webbert, R., Weidner, S., Weigle, G. E., II, White, O. L., Whittenburg, K., Williams, B. G., Williams, K., Williams, S., Woods, W. W., Zangari, A. M., and Zirnstein, E.

Published
2015
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10. TAOK1 is associated with neurodevelopmental disorder and essential for neuronal maturation and cortical development

Author

Woerden, G.M. van, Bos, M., Konink, C. de, Distel, B., Trezza, R. Avagliano, Shur, N.E., Barañano, K., Mahida, S., Chassevent, A., Schreiber, A., Erwin, A.L., Gripp, K.W., Rehman, F., Brulleman, S., McCormack, R., Geus, G. de, Kalsner, L., Sorlin, A., Bruel, A.L., Koolen, D.A., Gabriel, M.K., Rossi, M., Fitzpatrick, D.R., Wilkie, A.O.M., Calpena, E., Johnson, D., Brooks, A., Slegtenhorst, M. van, Fleischer, J., Groepper, D., Lindstrom, K., Innes, A. Micheil, Goodwin, A., Humberson, J., Noyes, A., Langley, K.G., Telegrafi, A., Blevins, A., Hoffman, J., Sacoto, M.J. Guillen, Juusola, J., Monaghan, K.G., Punj, S., Simon, M., Pfundt, R.P., Elgersma, Y., Kleefstra, T., Woerden, G.M. van, Bos, M., Konink, C. de, Distel, B., Trezza, R. Avagliano, Shur, N.E., Barañano, K., Mahida, S., Chassevent, A., Schreiber, A., Erwin, A.L., Gripp, K.W., Rehman, F., Brulleman, S., McCormack, R., Geus, G. de, Kalsner, L., Sorlin, A., Bruel, A.L., Koolen, D.A., Gabriel, M.K., Rossi, M., Fitzpatrick, D.R., Wilkie, A.O.M., Calpena, E., Johnson, D., Brooks, A., Slegtenhorst, M. van, Fleischer, J., Groepper, D., Lindstrom, K., Innes, A. Micheil, Goodwin, A., Humberson, J., Noyes, A., Langley, K.G., Telegrafi, A., Blevins, A., Hoffman, J., Sacoto, M.J. Guillen, Juusola, J., Monaghan, K.G., Punj, S., Simon, M., Pfundt, R.P., Elgersma, Y., and Kleefstra, T.

Abstract

Contains fulltext : 245113.pdf (Publisher’s version ) (Open Access), Thousand and one amino-acid kinase 1 (TAOK1) is a MAP3K protein kinase, regulating different mitogen-activated protein kinase pathways, thereby modulating a multitude of processes in the cell. Given the recent finding of TAOK1 involvement in neurodevelopmental disorders (NDDs), we investigated the role of TAOK1 in neuronal function and collected a cohort of 23 individuals with mostly de novo variants in TAOK1 to further define the associated NDD. Here, we provide evidence for an important role for TAOK1 in neuronal function, showing that altered TAOK1 expression levels in the embryonic mouse brain affect neural migration in vivo, as well as neuronal maturation in vitro. The molecular spectrum of the identified TAOK1 variants comprises largely truncating and nonsense variants, but also missense variants, for which we provide evidence that they can have a loss of function or dominant-negative effect on TAOK1, expanding the potential underlying causative mechanisms resulting in NDD. Taken together, our data indicate that TAOK1 activity needs to be properly controlled for normal neuronal function and that TAOK1 dysregulation leads to a neurodevelopmental disorder mainly comprising similar facial features, developmental delay/intellectual disability and/or variable learning or behavioral problems, muscular hypotonia, infant feeding difficulties, and growth problems.

Published
2021

11. SPEN haploinsufficiency causes a neurodevelopmental disorder overlapping proximal 1p36 deletion syndrome with an episignature of X chromosomes in females

Author

Radio, F.C., Pang, K., Ciolfi, A., Levy, M.A., Hernández-García, A., Pedace, L., Pantaleoni, F., Liu, Z, Boer, E. de, Jackson, A., Bruselles, A., McConkey, H., Stellacci, E., Cicero, S. Lo, Motta, M., Carrozzo, R., Dentici, M.L., McWalter, K., Desai, M., Monaghan, K.G., Telegrafi, A., Philippe, C., Vitobello, A., Au, M., Grand, K., Sanchez-Lara, P.A., Baez, J., Lindstrom, K., Kulch, P., Sebastian, J., Madan-Khetarpal, S., Roadhouse, C., MacKenzie, J.J., Monteleone, B., Saunders, C.J., Cuevas, J.K. Jean, Cross, L., Zhou, D., Hartley, T., Sawyer, S.L., Monteiro, F.P., Secches, T.V., Kok, F., Schultz-Rogers, L.E., Macke, E.L., Morava, E., Klee, E.W., Kemppainen, J., Iascone, M., Selicorni, A., Tenconi, R., Amor, D.J., Pais, L., Gallacher, L., Turnpenny, P.D., Stals, K., Ellard, S., Cabet, S., Lesca, G., Pascal, J., Steindl, K., Ravid, S., Weiss, K., Castle, A.M.R., Carter, M.T., Kalsner, L., Vries, B.B.A. de, Bon, B.W. van, Wevers, M.R., Pfundt, R.P., Stegmann, A.P.A., Kerr, B., Kingston, H.M., Chandler, K.E., Sheehan, W., Elias, A.F., Shinde, D.N., Towne, M.C., Robin, N.H., Goodloe, D., Vanderver, A., Sherbini, O., Bluske, K., Hagelstrom, R.T., Zanus, C., Faletra, F., Musante, L., Kurtz-Nelson, E.C., Earl, R.K., Anderlid, B.M., Morin, G., Slegtenhorst, M. van, Diderich, K.E.M., Brooks, A.S., Gribnau, J., Boers, R.G., Finestra, T.R., Carter, L.B., Rauch, A., Gasparini, P., Vissers, L.E.L.M., Lloyd Holder, J., Tartaglia, M., Radio, F.C., Pang, K., Ciolfi, A., Levy, M.A., Hernández-García, A., Pedace, L., Pantaleoni, F., Liu, Z, Boer, E. de, Jackson, A., Bruselles, A., McConkey, H., Stellacci, E., Cicero, S. Lo, Motta, M., Carrozzo, R., Dentici, M.L., McWalter, K., Desai, M., Monaghan, K.G., Telegrafi, A., Philippe, C., Vitobello, A., Au, M., Grand, K., Sanchez-Lara, P.A., Baez, J., Lindstrom, K., Kulch, P., Sebastian, J., Madan-Khetarpal, S., Roadhouse, C., MacKenzie, J.J., Monteleone, B., Saunders, C.J., Cuevas, J.K. Jean, Cross, L., Zhou, D., Hartley, T., Sawyer, S.L., Monteiro, F.P., Secches, T.V., Kok, F., Schultz-Rogers, L.E., Macke, E.L., Morava, E., Klee, E.W., Kemppainen, J., Iascone, M., Selicorni, A., Tenconi, R., Amor, D.J., Pais, L., Gallacher, L., Turnpenny, P.D., Stals, K., Ellard, S., Cabet, S., Lesca, G., Pascal, J., Steindl, K., Ravid, S., Weiss, K., Castle, A.M.R., Carter, M.T., Kalsner, L., Vries, B.B.A. de, Bon, B.W. van, Wevers, M.R., Pfundt, R.P., Stegmann, A.P.A., Kerr, B., Kingston, H.M., Chandler, K.E., Sheehan, W., Elias, A.F., Shinde, D.N., Towne, M.C., Robin, N.H., Goodloe, D., Vanderver, A., Sherbini, O., Bluske, K., Hagelstrom, R.T., Zanus, C., Faletra, F., Musante, L., Kurtz-Nelson, E.C., Earl, R.K., Anderlid, B.M., Morin, G., Slegtenhorst, M. van, Diderich, K.E.M., Brooks, A.S., Gribnau, J., Boers, R.G., Finestra, T.R., Carter, L.B., Rauch, A., Gasparini, P., Vissers, L.E.L.M., Lloyd Holder, J., and Tartaglia, M.

Abstract

Contains fulltext : 231702.pdf (Publisher’s version ) (Closed access), Deletion 1p36 (del1p36) syndrome is the most common human disorder resulting from a terminal autosomal deletion. This condition is molecularly and clinically heterogeneous. Deletions involving two non-overlapping regions, known as the distal (telomeric) and proximal (centromeric) critical regions, are sufficient to cause the majority of the recurrent clinical features, although with different facial features and dysmorphisms. SPEN encodes a transcriptional repressor commonly deleted in proximal del1p36 syndrome and is located centromeric to the proximal 1p36 critical region. Here, we used clinical data from 34 individuals with truncating variants in SPEN to define a neurodevelopmental disorder presenting with features that overlap considerably with those of proximal del1p36 syndrome. The clinical profile of this disease includes developmental delay/intellectual disability, autism spectrum disorder, anxiety, aggressive behavior, attention deficit disorder, hypotonia, brain and spine anomalies, congenital heart defects, high/narrow palate, facial dysmorphisms, and obesity/increased BMI, especially in females. SPEN also emerges as a relevant gene for del1p36 syndrome by co-expression analyses. Finally, we show that haploinsufficiency of SPEN is associated with a distinctive DNA methylation episignature of the X chromosome in affected females, providing further evidence of a specific contribution of the protein to the epigenetic control of this chromosome, and a paradigm of an X chromosome-specific episignature that classifies syndromic traits. We conclude that SPEN is required for multiple developmental processes and SPEN haploinsufficiency is a major contributor to a disorder associated with deletions centromeric to the previously established 1p36 critical regions.

Published
2021

12. Truncating SRCAP variants outside the Floating-Harbor syndrome locus cause a distinct neurodevelopmental disorder with a specific DNA methylation signature

Author

Rots, D., Chater-Diehl, E., Dingemans, A.J.M., Goodman, S.J., Siu, M.T., Cytrynbaum, C., Choufani, S., Hoang, N., Walker, S., Awamleh, Z., Charkow, J., Meyn, S., Pfundt, R.P., Rinne, T.K., Gardeitchik, T., Vries, B.B.A. de, Deden, A.C., Leenders, E.K.S.M., Kwint, M.P., Stumpel, C., Stevens, S.J.C., Vermeulen, J.R., Harssel, J.V.T. van, Bosch, D.G.M., Gassen, K.L.I. van, Binsbergen, E. van, Geus, C.M. de, Brackel, H., Hempel, M., Lessel, D., Denecke, J., Slavotinek, A., Strober, J., Crunk, A., Folk, L., Wentzensen, I.M., Yang, H., Zou, F., Millan, F., Person, R., Xie, Y., Liu, S., Ousager, L.B., Larsen, M., Schultz-Rogers, L., Morava, E., Klee, E.W., Berry, I.R., Campbell, J., Lindstrom, K., Pruniski, B., Neumeyer, A.M., Radley, J.A., Phornphutkul, C., Schmidt, B., Wilson, W.G., Õunap, K., Reinson, K., Pajusalu, S., Haeringen, A. van, Ruivenkamp, C., Cuperus, R., Santos-Simarro, F., Palomares-Bralo, M., Pacio-Míguez, M., Ritter, A., Bhoj, E., Tønne, E., Tveten, K., Cappuccio, G., Brunetti-Pierri, N., Rowe, L., Bunn, J., Saenz, M., Platzer, K., Mertens, M., Caluseriu, O., Nowaczyk, M.J., Cohn, R.D., Kannu, P., Alkhunaizi, E., Chitayat, D., Scherer, S.W., Brunner, H.G., Vissers, L.E., Kleefstra, T., Koolen, D.A., Weksberg, R., Rots, D., Chater-Diehl, E., Dingemans, A.J.M., Goodman, S.J., Siu, M.T., Cytrynbaum, C., Choufani, S., Hoang, N., Walker, S., Awamleh, Z., Charkow, J., Meyn, S., Pfundt, R.P., Rinne, T.K., Gardeitchik, T., Vries, B.B.A. de, Deden, A.C., Leenders, E.K.S.M., Kwint, M.P., Stumpel, C., Stevens, S.J.C., Vermeulen, J.R., Harssel, J.V.T. van, Bosch, D.G.M., Gassen, K.L.I. van, Binsbergen, E. van, Geus, C.M. de, Brackel, H., Hempel, M., Lessel, D., Denecke, J., Slavotinek, A., Strober, J., Crunk, A., Folk, L., Wentzensen, I.M., Yang, H., Zou, F., Millan, F., Person, R., Xie, Y., Liu, S., Ousager, L.B., Larsen, M., Schultz-Rogers, L., Morava, E., Klee, E.W., Berry, I.R., Campbell, J., Lindstrom, K., Pruniski, B., Neumeyer, A.M., Radley, J.A., Phornphutkul, C., Schmidt, B., Wilson, W.G., Õunap, K., Reinson, K., Pajusalu, S., Haeringen, A. van, Ruivenkamp, C., Cuperus, R., Santos-Simarro, F., Palomares-Bralo, M., Pacio-Míguez, M., Ritter, A., Bhoj, E., Tønne, E., Tveten, K., Cappuccio, G., Brunetti-Pierri, N., Rowe, L., Bunn, J., Saenz, M., Platzer, K., Mertens, M., Caluseriu, O., Nowaczyk, M.J., Cohn, R.D., Kannu, P., Alkhunaizi, E., Chitayat, D., Scherer, S.W., Brunner, H.G., Vissers, L.E., Kleefstra, T., Koolen, D.A., and Weksberg, R.

Abstract

Contains fulltext : 234078.pdf (Publisher’s version ) (Open Access), Truncating variants in exons 33 and 34 of the SNF2-related CREBBP activator protein (SRCAP) gene cause the neurodevelopmental disorder (NDD) Floating-Harbor syndrome (FLHS), characterized by short stature, speech delay, and facial dysmorphism. Here, we present a cohort of 33 individuals with clinical features distinct from FLHS and truncating (mostly de novo) SRCAP variants either proximal (n = 28) or distal (n = 5) to the FLHS locus. Detailed clinical characterization of the proximal SRCAP individuals identified shared characteristics: developmental delay with or without intellectual disability, behavioral and psychiatric problems, non-specific facial features, musculoskeletal issues, and hypotonia. Because FLHS is known to be associated with a unique set of DNA methylation (DNAm) changes in blood, a DNAm signature, we investigated whether there was a distinct signature associated with our affected individuals. A machine-learning model, based on the FLHS DNAm signature, negatively classified all our tested subjects. Comparing proximal variants with typically developing controls, we identified a DNAm signature distinct from the FLHS signature. Based on the DNAm and clinical data, we refer to the condition as "non-FLHS SRCAP-related NDD." All five distal variants classified negatively using the FLHS DNAm model while two classified positively using the proximal model. This suggests divergent pathogenicity of these variants, though clinically the distal group presented with NDD, similar to the proximal SRCAP group. In summary, for SRCAP, there is a clear relationship between variant location, DNAm profile, and clinical phenotype. These results highlight the power of combined epigenetic, molecular, and clinical studies to identify and characterize genotype-epigenotype-phenotype correlations.

Published
2021

13. Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with Wiedemann-Steiner syndrome

Author

Sheppard, SE, Campbell, IM, Harr, MH, Gold, N, Li, D, Bjornsson, HT, Cohen, JS, Fahrner, JA, Fatemi, A, Harris, JR, Nowak, C, Stevens, CA, Grand, K, Au, M, Graham, JM, Sanchez-Lara, PA, Del Campo, M, Jones, MC, Abdul-Rahman, O, Alkuraya, FS, Bassetti, JA, Bergstrom, K, Bhoj, E, Dugan, S, Kaplan, JD, Derar, N, Gripp, KW, Hauser, N, Innes, AM, Keena, B, Kodra, N, Miller, R, Nelson, B, Nowaczyk, MJ, Rahbeeni, Z, Ben-Shachar, S, Shieh, JT, Slavotinek, A, Sobering, AK, Abbott, M-A, Allain, DC, Amlie-Wolf, L, Au, PYB, Bedoukian, E, Beek, G, Barry, J, Berg, J, Bernstein, JA, Cytrynbaum, C, Chung, BH-Y, Donoghue, S, Dorrani, N, Eaton, A, Flores-Daboub, JA, Dubbs, H, Felix, CA, Fong, C-T, Fung, JLF, Gangaram, B, Goldstein, A, Greenberg, R, Ha, TK, Hersh, J, Izumi, K, Kallish, S, Kravets, E, Kwok, P-Y, Jobling, RK, Johnson, AEK, Kushner, J, Lee, BH, Levin, B, Lindstrom, K, Manickam, K, Mardach, R, McCormick, E, McLeod, DR, Mentch, FD, Minks, K, Muraresku, C, Nelson, SF, Porazzi, P, Pichurin, PN, Powell-Hamilton, NN, Powis, Z, Ritter, A, Rogers, C, Rohena, L, Ronspies, C, Schroeder, A, Stark, Z, Starr, L, Stoler, J, Suwannarat, P, Velinov, M, Weksberg, R, Wilnai, Y, Zadeh, N, Zand, DJ, Falk, MJ, Hakonarson, H, Zackai, EH, Quintero-Rivera, F, Sheppard, SE, Campbell, IM, Harr, MH, Gold, N, Li, D, Bjornsson, HT, Cohen, JS, Fahrner, JA, Fatemi, A, Harris, JR, Nowak, C, Stevens, CA, Grand, K, Au, M, Graham, JM, Sanchez-Lara, PA, Del Campo, M, Jones, MC, Abdul-Rahman, O, Alkuraya, FS, Bassetti, JA, Bergstrom, K, Bhoj, E, Dugan, S, Kaplan, JD, Derar, N, Gripp, KW, Hauser, N, Innes, AM, Keena, B, Kodra, N, Miller, R, Nelson, B, Nowaczyk, MJ, Rahbeeni, Z, Ben-Shachar, S, Shieh, JT, Slavotinek, A, Sobering, AK, Abbott, M-A, Allain, DC, Amlie-Wolf, L, Au, PYB, Bedoukian, E, Beek, G, Barry, J, Berg, J, Bernstein, JA, Cytrynbaum, C, Chung, BH-Y, Donoghue, S, Dorrani, N, Eaton, A, Flores-Daboub, JA, Dubbs, H, Felix, CA, Fong, C-T, Fung, JLF, Gangaram, B, Goldstein, A, Greenberg, R, Ha, TK, Hersh, J, Izumi, K, Kallish, S, Kravets, E, Kwok, P-Y, Jobling, RK, Johnson, AEK, Kushner, J, Lee, BH, Levin, B, Lindstrom, K, Manickam, K, Mardach, R, McCormick, E, McLeod, DR, Mentch, FD, Minks, K, Muraresku, C, Nelson, SF, Porazzi, P, Pichurin, PN, Powell-Hamilton, NN, Powis, Z, Ritter, A, Rogers, C, Rohena, L, Ronspies, C, Schroeder, A, Stark, Z, Starr, L, Stoler, J, Suwannarat, P, Velinov, M, Weksberg, R, Wilnai, Y, Zadeh, N, Zand, DJ, Falk, MJ, Hakonarson, H, Zackai, EH, and Quintero-Rivera, F

Abstract

Wiedemann-Steiner syndrome (WSS) is an autosomal dominant disorder caused by monoallelic variants in KMT2A and characterized by intellectual disability and hypertrichosis. We performed a retrospective, multicenter, observational study of 104 individuals with WSS from five continents to characterize the clinical and molecular spectrum of WSS in diverse populations, to identify physical features that may be more prevalent in White versus Black Indigenous People of Color individuals, to delineate genotype-phenotype correlations, to define developmental milestones, to describe the syndrome through adulthood, and to examine clinicians' differential diagnoses. Sixty-nine of the 82 variants (84%) observed in the study were not previously reported in the literature. Common clinical features identified in the cohort included: developmental delay or intellectual disability (97%), constipation (63.8%), failure to thrive (67.7%), feeding difficulties (66.3%), hypertrichosis cubiti (57%), short stature (57.8%), and vertebral anomalies (46.9%). The median ages at walking and first words were 20 months and 18 months, respectively. Hypotonia was associated with loss of function (LoF) variants, and seizures were associated with non-LoF variants. This study identifies genotype-phenotype correlations as well as race-facial feature associations in an ethnically diverse cohort, and accurately defines developmental trajectories, medical comorbidities, and long-term outcomes in individuals with WSS.

Published
2021

14. Pathogenic variants in SMARCA5, a chromatin remodeler, cause a range of syndromic neurodevelopmental features

Author

Li, D, Wang, Q, Gong, NN, Kurolap, A, Feldman, HB, Boy, N, Brugger, M, Grand, K, McWalter, K, Sacoto, MJG, Wakeling, E, Hurst, J, March, ME, Bhoj, EJ, Nowaczyk, MJM, Gonzaga-Jauregui, C, Mathew, M, Dava-Wala, A, Siemon, A, Bartholomew, D, Huang, Y, Lee, H, Martinez-Agosto, JA, Schwaibold, EMC, Brunet, T, Choukair, D, Pais, LS, White, SM, Christodoulou, J, Brown, D, Lindstrom, K, Grebe, T, Tiosano, D, Kayser, MS, Tan, TY, Deardorff, MA, Song, Y, Hakonarson, H, Li, D, Wang, Q, Gong, NN, Kurolap, A, Feldman, HB, Boy, N, Brugger, M, Grand, K, McWalter, K, Sacoto, MJG, Wakeling, E, Hurst, J, March, ME, Bhoj, EJ, Nowaczyk, MJM, Gonzaga-Jauregui, C, Mathew, M, Dava-Wala, A, Siemon, A, Bartholomew, D, Huang, Y, Lee, H, Martinez-Agosto, JA, Schwaibold, EMC, Brunet, T, Choukair, D, Pais, LS, White, SM, Christodoulou, J, Brown, D, Lindstrom, K, Grebe, T, Tiosano, D, Kayser, MS, Tan, TY, Deardorff, MA, Song, Y, and Hakonarson, H

Abstract

Intellectual disability encompasses a wide spectrum of neurodevelopmental disorders, with many linked genetic loci. However, the underlying molecular mechanism for more than 50% of the patients remains elusive. We describe pathogenic variants in SMARCA5, encoding the ATPase motor of the ISWI chromatin remodeler, as a cause of a previously unidentified neurodevelopmental disorder, identifying 12 individuals with de novo or dominantly segregating rare heterozygous variants. Accompanying phenotypes include mild developmental delay, frequent postnatal short stature and microcephaly, and recurrent dysmorphic features. Loss of function of the SMARCA5 Drosophila ortholog Iswi led to smaller body size, reduced sensory dendrite complexity, and tiling defects in larvae. In adult flies, Iswi neural knockdown caused decreased brain size, aberrant mushroom body morphology, and abnormal locomotor function. Iswi loss of function was rescued by wild-type but not mutant SMARCA5. Our results demonstrate that SMARCA5 pathogenic variants cause a neurodevelopmental syndrome with mild facial dysmorphia.

Published
2021

15. Location, location, location: protein truncating variants in different loci of SRCAP cause three distinct neurodevelopmental disorders, associated with distinctive DNA methylation signatures

Author

Rots, D., Chater-Diehl, E., Dingemans, A. J. M., Siu, M., Cytrynbaum, C., Hoang, N., Walker, S., Scherer, S., Pfundt, R., Rinne, T., Gardeitchik, T., Vries, B. B. A., Stumpel, C. T. R. M., Stevens, S. J. C., Harssel, J., Bosch, D. G. M., Gassen, K. L. I., Binsbergen, E., Geus, C. M., Hempel, M., Lessel, D., Denecke, J., Slavotinek, A., Strober, J., Lilian Bomme Ousager, Martin Jakob Larsen, Schultz-Rogers, L., Morava, E., Klee, E. W., Berry, I. R., Campbell, J., Lindstrom, K., Neumeyer, A. M., Radley, J. A., Phornphutkul, C., Wilson, W. G., Schmidt, B., Meyn, S., Ounap, K., Reinson, K., Pajusalu, S., Ruivenkamp, C., Haeringen, A., Cuperus, R., Vissers, L. E. L. M., Brunner, H. G., Kleefstra, T., Koolen, D. A., Weksberg, R., and GeneDx Inc

Published
2020

16. Towards a learning organization: the introduction of a client-centered team-based organization in administrative surveying work

Author

Gard, G., Lindstrom, K., and Dallner, M.

Subjects
Job satisfaction, Surveying -- Research, Surveying -- Management, Company business management, Engineering and manufacturing industries, Health, Human resources and labor relations
Abstract

Within administrative surveying work in Sweden, a transition to a client-centered team-based organization was made during 1998. The aim of this study was to describe the employees' perceptions and expectations of job and organizational practices when working as a generalist in a client-centered team-based organization; job and organizational practices and well-being and effectiveness measures were examined when introducing a team-based organization. Interventions such as courses in how to cope with the role of a generalist, how to increase service to clients, education in technology, law and economics, as well as computer information support, were ongoing at the time of the study. The Team Work Profile and QPS Nordic questionnaires were used. All the surveyors in five regions in Sweden participated, in total 640 surveyors. The transition to a client-centered team-based organization was expected to improve job control and job content but at the same time lead to impairments in job climate and group cohesion. Distress was associated with negative future expectations of the organization. High job control and group cohesion were the central contributors towards growth in personal competence and social effectiveness of teamwork. Both internal and external client-related activities of team and organization were in focus during the transition. Keywords: Team; Work organization; Client-Centration; Administrative work

Published
2003

19. Effect of hydrolyzed infant formula vs conventional formula on risk of type 1 diabetes the TRIGR randomized clinical trial

Author

Knip M., Akerblom H. K., Altaji E., Becker D., Bruining J., Castano L., Danne T., De Beaufort C., Dosch H. -M., Dupre J., Fraser W. D., Howard N., Ilonen J., Konrad D., Kordonouri O., Krischer J. P., Lawson M. L., Ludvigsson J., Madacsy L., Mahon J. L., Ormisson A., Palmer J. P., Pozzilli P., Savilahti E., Serrano-Rios M., Songini M., Taback S., Vaarala O., White N. H., Virtanen S. M., Wasikowa R., Mandrup-Poulsen T., Arjas E., Lernmark A., Laara E., Schmidt B., Hyytinen M., Koski K., Koski M., Merentie K., Pajakkala E., Reunanen A., Salonen M., Terhonen T., Virkkunen S., Cuthbertson D., Gainer B., Hadley D., Malloy J., Nallamshetty L., Shanker L., Bradley B., Lough G., Fraser W., Sermer M., Taback S. P., Franciscus M., Nucci A., Palmer J., Alahuhta K., Barlund S., Korhonen T., Kovanen L., Lehtonen E., Niinisto S., Pekkala M., Sorkio S., Toivanen L., Vahatalo L., Uusitalo U., Ohman T., Bongiorno R., Catteau J., Fraser G., Lloyd M., Crock P., Giles M., Siech K., See D. W., Brown C., Craig M., Johnston A., Bere L. J., Clarson C. L., Jenner M., McManus R., Renato N., Lovell M., Higo D., Kent N., Kwan J., Marshall C., Metzger D., Chanoine J. -P., Stewart L., Thompson D., Edwards A., Lange I., Mercer J., Pacaud D., Josephine H., Schwarz W., Stephure D. K., Boer J., Chatur T., Chick C., Couch B., Demianczuk N., Girgis R., Marks S., Ryan E., Thompson M., Dean H. J., Grant L., Hamelin K., LaForte J., Murphy L., Catte D., Schneider C., Sellers E. A. C., Woo V., Boland A., Clark H. D., Cooper T., Gruslin A., Karovitch A., Keely E., Malcolm J. C., Sauro V., Tawagi G. F., Andrighetti S., Arnold G., Barrett J., Blumer I., Daneman D., Donat D., Ehrlich R., Feig D., Gottesman I., Gysler M., Karkanis S., Kenshole A., Knight B., Lackie E., Lewis V., Martin M. J., Maxwell C., Oliver G., Panchum P., Shilletto N., Simone A., Skidmore M., Turrini T., Wong S., Allen C., Belanger L., Bouchard I., Ferland S., Frenette L., Garrido-Russo M., Leblanc M., Imbeault J., Morin V., Olivier G., Weisnagell J., Costain G., Dornan J., Heath K., MacSween M. -C., McGibbon A., Ramsay C., Sanderson F., Sanderson S., Benabdesselam L., Gonthier M., Huot C., Thibeault M., Laforte D., Legault L., Perron P., Armson A., Canning P., Cummings E. A., Ivanko V., McLeod L., Mokashi A., Scott K., Bridger T., Crane J., Crummell C., Curtis J. C., Dawson C., Joyce C., Newhook L. A., Newman S., Druken E., Begum-Hasan J., Breen A., Houlden R., Woods M., Carrson G., Kelly S., Martel M. J., Penner M., Sankaran K., Hardy-Brown K., King N., White R. A., Park M., Popkin J., Robson L., Coles K., Al Taji E., Cerna M., Cerny M., Francova H., Hainerova I., Kothankova H., Koukalova R., Krakorova V., Mendlova P., Sitova R., Stechova K., Vavrinec J., Vosahlo J., Zlatohlavkova B., Brazdova L., Faksova P., Gregorova D., Kantor L., Malkova K., Venhacova J., Venhacova P., Cipra A., Skvor J., Budejovice C., Tomsikova Z., Botkova-Krauseova H., Mockova A., Paterova P., Gogelova P., Kandrnalova J., Einberg U., Jakovlev U., Posiadlo S., Rannaste E., Raukas R., Riikjarv M. -A., Valla K., Astover V., Kirss A., Retpap J., Taht E., Tillmann V., Vahtra S., Heikkila M., Hirvasniemi M., Luopajarvi K., Johansson S., Kleemola P., Laukkanen E., Parkkola A., Pigg H. -M., Puttonen H., Renlund M., Salonen K., Suomalainen H., Tenkula T., Teramo K., Jarvenpaa A. -L., Hamalainen A. -M., Jussila R., Kiiveri S., Haavisto H., Holopainen S., Kupiainen H., Leeve T., Lumme K., Nironen T., Tenhola S., Tiilikainen T., Keinonen H., Lautala P., Salonen P., Vesanto M., Aspholm A. S., Asunta P., Ikavalko H., Jason E., Jaminki S., Kekki P., Koskinen M., Lehtimaki S., Lahde J., Makela M., Peltoniemi S., Poutiainen L., Ranta K., Salonsaari T., Sarviharju-Tujula S. -L., Selvenius J., Siljander H., Haanpaa P. -L., Holm C., Juutilainen A., Jarvelainen V., Kangaskolkka-Keskilohko A. -M., Laino E., Marjamaki L., Suominen E., Ylitalo S., Hokkanen M., Lounamaa R., Matikainen M., Nuuja A., Paalanen I., Puupponen A. R., Salo-Edwards H., Alanne S., Kultti T., Linjama H., Muhonen K., Vaaraniemi M., Talvitie T., Backman M., Hanhijarvi R., Koivula P., Lindstrom K., Martikainen A., Nurmi P., Bjork A., Huopio H., Komulainen J., Lehtomaki S., Muikku E., Pesola J., Sankilampi U., Arkkola T., Hekkala A., Jurvakainen S., Koivikko M. -L., Kahonen M., Leinonen E., Mykkanen T., Pohjola H., Riikonen K., Niittyvuopio A., Stenius A., Tapanainen P., Veijola R., Alar A., Jovio S., Korpela P., Makinen E., Hietanen L., Kivisto J., Kaar M. -L., Lehtimaki P., Mustila T., Popov E., Saatela S., Taittonen L., Ahtiainen K., Laaksonen N., Luoto M., Viitala J., Virransalo R., Nykanen P., Paajanen S., Parkkinen S., Pyrhonen H., Sarkka T., Aschemeier B., Bektas S., Biester T., Datz N., Deiss D., Fath M., Lupke K., Muller B., Nestoris C., Rothes S., Sadeghian E., Semler K., Arato A., Krikovszky D., Nobilis A., Szenasi J., Benevento D., Anguissola G. B., Biagioni M., Bizzarri C., Cherubini V., Ferrito L., Giordano C., Giorgetti C., Khazrai Y. M., Kyanvash S., Maddaloni E., Napoli A., Piergiovanni F., Pitocco D., Suraci T., Tabacco G., Valente L., Visalli N., Carboni M. B., Cavallo R., Cau V., Isola C., Ledda A., Loddo M., Mannu C., Pettinau M., Pisano S., Porceddu M., Putzu C., Rita A., Peters D., Schierloh U., Bisschoff M., Blonk L., Lappenschaar T., Manai B., Seesink M., Sperling-Conrad M., Verhagen M., Zoethout J. A., Basiak A., Chalas M., Chesiak M., Gramza A., Iwankiewicz J., Sieradzan E., Wikiera B., Ciechanowska M., Dziatkowiak H., Futona B., Gorska A., Glowacka-Wony M., Kaim I., Klich B., Starzyk J., Wolanin M., Tokarska L., Chucherco D., Deja G., Firek-Pedras M., Jarosz-Chobot P., Kalina M., Kutrowska-Adamusiak K., Minkina-Pedras M., Muchaka-Bianga M., Bodalski J., Mlynarski W., Szadkowska A., Cieslak A., Cypryk K., Dziatosz K., Jastzebowska J., Krysiak A., Szymanska U., Wilcznski J., Zawodniak-Szalapska M., Aguay A., Bilbao J. R., Chueca M., Cortazar A., Echarte G., Frutos T. G., Jimenez P., Martul P., Moreno A., Oyarzabal M., Rica I., Salgado Y., Martinez-Larrad M. T., Hawkins F. G., Hernandez R., Herranz L., Pallardo L. F., Deibarra L. S., Fernandez B. H., Luis J. L., Ortiz-Quintana L., Recarte P. P., Arnau D. R., Aronsson L., Boden S., Fredriksson J., Isacsson E., Johansson I., Karlsson E., Lock C., Sandstrom A. -M., Konefal M. S., Andreasson C., Dahlstrom U., Hanas R., Lundqvist K., Windell L., Jansson I., Karlsson A. -K., Lindbladh B., Odenman I., Pettersson C., Sundberg F., Sundqvist M., Aronsson S., Bellman I., Bengtsson A. -B., Lyden G. -B., Nilsson N. -O., Soderblom M., Unt C., Augustsson M., Bengtsson M., Fors H., Helmrich A., Johansson T. O., Andersson A. -C., Boiard-Stomlid A., Hellgren G., Kallsholm H., Lindqvist J., Nilsson M., Nordwall M., Stromstedt C., Ahsberg C., Lindh A., Lindhe C., Samuelsson C., Wiik A., Edenwall H., Ljumgcrantz M., Persson I. -B., Strigard E., Svensson B. -L., Aman J., Breivik G. -E., Detlofsson I. -L., Kroon M., Sarnblad S., Johansson C., Ilvered R., Lundberg A., Akesson K., Beccarelli A., Gadient M., Rappold-Amrein C., Schoenle E., Daftary A., Damagro-Elias M. E., Gilmour C., Klein M. B., Lain C., Salerno D., Smith M. E., Vats K., Pfaff D. J., Malone P., Mansfield P., Munns M., Nickel K., Pompilio K., Siemion W., Taculad R., Van Horn K., Zdanadewic M., Chambliss C., Jones J., Sadler M., Tanner-Blasiar M., Bell C., Camper N., Devaskar S., Devaskar U., Horowitz H., Rogers L., Shannahan R., Silk K., Bermudez Z., Colon R., Frazer T., Martinez-Nieves B., Torres J., Vega J., Chan M., Cook S., Goland R., Greenberg E., Jules N., Montes J., Nelson M., Parra-Valencia Z., Schachner H., Softness B., Kiviniemi M., Suomenin R., Alexander A., Hyrckowian E., Nichol L., Trucco M., Karjalainen E., Louhio T., Sarnesto A., Valtonen E., Davydova B., Helander S., Hamalainen J., Harkonen T., Joutsjoki L., Kararic M., Latva-Koivisto M., Lonn E., Nurmi T., Ollila I., Rinkinen J., Ronkainen M., Tukiainen H., Cederlof A., Kiikeri M., Tsupari S., Cheng R., Bryant K., Chan Y., Maezawa Y., Paltser G., Rasavi R., Tsui H., Winer S., Wu P., Yantha J., Pediatrics, Knip M., Akerblom H.K., Altaji E., Becker D., Bruining J., Castano L., Danne T., De Beaufort C., Dosch H.-M., Dupre J., Fraser W.D., Howard N., Ilonen J., Konrad D., Kordonouri O., Krischer J.P., Lawson M.L., Ludvigsson J., Madacsy L., Mahon J.L., Ormisson A., Palmer J.P., Pozzilli P., Savilahti E., Serrano-Rios M., Songini M., Taback S., Vaarala O., White N.H., Virtanen S.M., Wasikowa R., Mandrup-Poulsen T., Arjas E., Lernmark A., Laara E., Schmidt B., Hyytinen M., Koski K., Koski M., Merentie K., Pajakkala E., Reunanen A., Salonen M., Terhonen T., Virkkunen S., Cuthbertson D., Gainer B., Hadley D., Malloy J., Nallamshetty L., Shanker L., Bradley B., Lough G., Fraser W., Sermer M., Taback S.P., Franciscus M., Nucci A., Palmer J., Alahuhta K., Barlund S., Korhonen T., Kovanen L., Lehtonen E., Niinisto S., Pekkala M., Sorkio S., Toivanen L., Vahatalo L., Uusitalo U., Ohman T., Bongiorno R., Catteau J., Fraser G., Lloyd M., Crock P., Giles M., Siech K., See D.W., Brown C., Craig M., Johnston A., Bere L.J., Clarson C.L., Jenner M., McManus R., Renato N., Lovell M., Higo D., Kent N., Kwan J., Marshall C., Metzger D., Chanoine J.-P., Stewart L., Thompson D., Edwards A., Lange I., Mercer J., Pacaud D., Josephine H., Schwarz W., Stephure D.K., Boer J., Chatur T., Chick C., Couch B., Demianczuk N., Girgis R., Marks S., Ryan E., Thompson M., Dean H.J., Grant L., Hamelin K., LaForte J., Murphy L., Catte D., Schneider C., Sellers E.A.C., Woo V., Boland A., Clark H.D., Cooper T., Gruslin A., Karovitch A., Keely E., Malcolm J.C., Sauro V., Tawagi G.F., Andrighetti S., Arnold G., Barrett J., Blumer I., Daneman D., Donat D., Ehrlich R., Feig D., Gottesman I., Gysler M., Karkanis S., Kenshole A., Knight B., Lackie E., Lewis V., Martin M.J., Maxwell C., Oliver G., Panchum P., Shilletto N., Simone A., Skidmore M., Turrini T., Wong S., Allen C., Belanger L., Bouchard I., Ferland S., Frenette L., Garrido-Russo M., Leblanc M., Imbeault J., Morin V., Olivier G., Weisnagell J., Costain G., Dornan J., Heath K., MacSween M.-C., McGibbon A., Ramsay C., Sanderson F., Sanderson S., Benabdesselam L., Gonthier M., Huot C., Thibeault M., Laforte D., Legault L., Perron P., Armson A., Canning P., Cummings E.A., Ivanko V., McLeod L., Mokashi A., Scott K., Bridger T., Crane J., Crummell C., Curtis J.C., Dawson C., Joyce C., Newhook L.A., Newman S., Druken E., Begum-Hasan J., Breen A., Houlden R., Woods M., Carrson G., Kelly S., Martel M.J., Penner M., Sankaran K., Hardy-Brown K., King N., White R.A., Park M., Popkin J., Robson L., Coles K., Al Taji E., Cerna M., Cerny M., Francova H., Hainerova I., Kothankova H., Koukalova R., Krakorova V., Mendlova P., Sitova R., Stechova K., Vavrinec J., Vosahlo J., Zlatohlavkova B., Brazdova L., Faksova P., Gregorova D., Kantor L., Malkova K., Venhacova J., Venhacova P., Cipra A., Skvor J., Budejovice C., Tomsikova Z., Botkova-Krauseova H., Mockova A., Paterova P., Gogelova P., Kandrnalova J., Einberg U., Jakovlev U., Posiadlo S., Rannaste E., Raukas R., Riikjarv M.-A., Valla K., Astover V., Kirss A., Retpap J., Taht E., Tillmann V., Vahtra S., Heikkila M., Hirvasniemi M., Luopajarvi K., Johansson S., Kleemola P., Laukkanen E., Parkkola A., Pigg H.-M., Puttonen H., Renlund M., Salonen K., Suomalainen H., Tenkula T., Teramo K., Jarvenpaa A.-L., Hamalainen A.-M., Jussila R., Kiiveri S., Haavisto H., Holopainen S., Kupiainen H., Leeve T., Lumme K., Nironen T., Tenhola S., Tiilikainen T., Keinonen H., Lautala P., Salonen P., Vesanto M., Aspholm A.S., Asunta P., Ikavalko H., Jason E., Jaminki S., Kekki P., Koskinen M., Lehtimaki S., Lahde J., Makela M., Peltoniemi S., Poutiainen L., Ranta K., Salonsaari T., Sarviharju-Tujula S.-L., Selvenius J., Siljander H., Haanpaa P.-L., Holm C., Juutilainen A., Jarvelainen V., Kangaskolkka-Keskilohko A.-M., Laino E., Marjamaki L., Suominen E., Ylitalo S., Hokkanen M., Lounamaa R., Matikainen M., Nuuja A., Paalanen I., Puupponen A.R., Salo-Edwards H., Alanne S., Kultti T., Linjama H., Muhonen K., Vaaraniemi M., Talvitie T., Backman M., Hanhijarvi R., Koivula P., Lindstrom K., Martikainen A., Nurmi P., Bjork A., Huopio H., Komulainen J., Lehtomaki S., Muikku E., Pesola J., Sankilampi U., Arkkola T., Hekkala A., Jurvakainen S., Koivikko M.-L., Kahonen M., Leinonen E., Mykkanen T., Pohjola H., Riikonen K., Niittyvuopio A., Stenius A., Tapanainen P., Veijola R., Alar A., Jovio S., Korpela P., Makinen E., Hietanen L., Kivisto J., Kaar M.-L., Lehtimaki P., Mustila T., Popov E., Saatela S., Taittonen L., Ahtiainen K., Laaksonen N., Luoto M., Viitala J., Virransalo R., Nykanen P., Paajanen S., Parkkinen S., Pyrhonen H., Sarkka T., Aschemeier B., Bektas S., Biester T., Datz N., Deiss D., Fath M., Lupke K., Muller B., Nestoris C., Rothes S., Sadeghian E., Semler K., Arato A., Krikovszky D., Nobilis A., Szenasi J., Benevento D., Anguissola G.B., Biagioni M., Bizzarri C., Cherubini V., Ferrito L., Giordano C., Giorgetti C., Khazrai Y.M., Kyanvash S., Maddaloni E., Napoli A., Piergiovanni F., Pitocco D., Suraci T., Tabacco G., Valente L., Visalli N., Carboni M.B., Cavallo R., Cau V., Isola C., Ledda A., Loddo M., Mannu C., Pettinau M., Pisano S., Porceddu M., Putzu C., Rita A., Peters D., Schierloh U., Bisschoff M., Blonk L., Lappenschaar T., Manai B., Seesink M., Sperling-Conrad M., Verhagen M., Zoethout J.A., Basiak A., Chalas M., Chesiak M., Gramza A., Iwankiewicz J., Sieradzan E., Wikiera B., Ciechanowska M., Dziatkowiak H., Futona B., Gorska A., Glowacka-Wony M., Kaim I., Klich B., Starzyk J., Wolanin M., Tokarska L., Chucherco D., Deja G., Firek-Pedras M., Jarosz-Chobot P., Kalina M., Kutrowska-Adamusiak K., Minkina-Pedras M., Muchaka-Bianga M., Bodalski J., Mlynarski W., Szadkowska A., Cieslak A., Cypryk K., Dziatosz K., Jastzebowska J., Krysiak A., Szymanska U., Wilcznski J., Zawodniak-Szalapska M., Aguay A., Bilbao J.R., Chueca M., Cortazar A., Echarte G., Frutos T.G., Jimenez P., Martul P., Moreno A., Oyarzabal M., Rica I., Salgado Y., Martinez-Larrad M.T., Hawkins F.G., Hernandez R., Herranz L., Pallardo L.F., Deibarra L.S., Fernandez B.H., Luis J.L., Ortiz-Quintana L., Recarte P.P., Arnau D.R., Aronsson L., Boden S., Fredriksson J., Isacsson E., Johansson I., Karlsson E., Lock C., Sandstrom A.-M., Konefal M.S., Andreasson C., Dahlstrom U., Hanas R., Lundqvist K., Windell L., Jansson I., Karlsson A.-K., Lindbladh B., Odenman I., Pettersson C., Sundberg F., Sundqvist M., Aronsson S., Bellman I., Bengtsson A.-B., Lyden G.-B., Nilsson N.-O., Soderblom M., Unt C., Augustsson M., Bengtsson M., Fors H., Helmrich A., Johansson T.O., Andersson A.-C., Boiard-Stomlid A., Hellgren G., Kallsholm H., Lindqvist J., Nilsson M., Nordwall M., Stromstedt C., Ahsberg C., Lindh A., Lindhe C., Samuelsson C., Wiik A., Edenwall H., Ljumgcrantz M., Persson I.-B., Strigard E., Svensson B.-L., Aman J., Breivik G.-E., Detlofsson I.-L., Kroon M., Sarnblad S., Johansson C., Ilvered R., Lundberg A., Akesson K., Beccarelli A., Gadient M., Rappold-Amrein C., Schoenle E., Daftary A., Damagro-Elias M.E., Gilmour C., Klein M.B., Lain C., Salerno D., Smith M.E., Vats K., Pfaff D.J., Malone P., Mansfield P., Munns M., Nickel K., Pompilio K., Siemion W., Taculad R., Van Horn K., Zdanadewic M., Chambliss C., Jones J., Sadler M., Tanner-Blasiar M., Bell C., Camper N., Devaskar S., Devaskar U., Horowitz H., Rogers L., Shannahan R., Silk K., Bermudez Z., Colon R., Frazer T., Martinez-Nieves B., Torres J., Vega J., Chan M., Cook S., Goland R., Greenberg E., Jules N., Montes J., Nelson M., Parra-Valencia Z., Schachner H., Softness B., Kiviniemi M., Suomenin R., Alexander A., Hyrckowian E., Nichol L., Trucco M., Karjalainen E., Louhio T., Sarnesto A., Valtonen E., Davydova B., Helander S., Hamalainen J., Harkonen T., Joutsjoki L., Kararic M., Latva-Koivisto M., Lonn E., Nurmi T., Ollila I., Rinkinen J., Ronkainen M., Tukiainen H., Cederlof A., Kiikeri M., Tsupari S., Cheng R., Bryant K., Chan Y., Maezawa Y., Paltser G., Rasavi R., Tsui H., Winer S., Wu P., Yantha J., University of Zurich, and Knip, Mikael

Subjects
Male, Risk, medicine.medical_specialty, Casein, Breastfeeding, 030209 endocrinology & metabolism, 610 Medicine & health, 2700 General Medicine, Endocrinology and Diabetes, Disease-Free Survival, law.invention, Follow-Up Studie, Nutrition Policy, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Double-Blind Method, SDG 3 - Good Health and Well-being, law, Internal medicine, Diabetes mellitus, medicine, Humans, Cumulative incidence, 030212 general & internal medicine, Child, Infant Nutritional Physiological Phenomena, Original Investigation, 2. Zero hunger, Type 1 diabetes, business.industry, Hazard ratio, Absolute risk reduction, Infant, Newborn, Caseins, General Medicine, ta3121, medicine.disease, Infant Formula, 3. Good health, Diabetes Mellitus, Type 1, Infant formula, 10036 Medical Clinic, Endokrinologi och diabetes, Female, business, Human, Follow-Up Studies
Abstract

IMPORTANCE Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children. DESIGN, SETTING, AND PARTICIPANTS An international double-blind randomized clinical trial of 2159 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1081 were randomized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula. The follow-up of the participants ended on February 28, 2017. INTERVENTIONS The participants received either a casein hydrolysate or a conventional adapted cows milk formula supplemented with 20% of the casein hydrolysate. The minimum duration of study formula exposure was 60 days by 6 to 8 months of age. MAIN OUTCOMES AND MEASURES Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). RESULTS Among 2159 newborn infants (1021 female [47.3%]) who were randomized, 1744 (80.8%) completed the trial. The participants were observed for a median of 11.5 years (quartile [Q] 1-Q3, 10.2-12.8). The absolute risk of type 1 diabetes was 8.4% among those randomized to the casein hydrolysate (n = 91) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8%[95% CI, -1.6% to 3.2%]). The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 1.1 (95% CI, 0.8 to 1.5; P = .46). The median age at diagnosis of type 1 diabetes was similar in the 2 groups (6.0 years [Q1-Q3, 3.1-8.9] vs 5.8 years [Q1-Q3, 2.6-9.1]; difference, 0.2 years [95% CI, -0.9 to 1.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). CONCLUSIONS AND RELEVANCE Among infants at risk for type 1 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes. Funding Agencies|Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD); National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health [HD040364, HD042444, HD051997]; Canadian Institutes of Health Research; Commission of the European Communities [QLK1-2002-00372]; European Foundation for the Study of Diabates/JDRF/Novo Nordisk; Academy of Finland (Centre of Excellence in Molecular Systems Immunology and Physiology Research) [250114]; Dutch Diabetes Research Foundation; Finnish Diabetes Research Foundation; JDRF

Published
2018

20. The landscape of epilepsy-related GATOR1 variants (vol 21, pg 398, 2019)

Author

Baldassari, S., Picard, F., Verbeek, N.E., Kempen, M. van, Brilstra, E.H., Lesca, G., Conti, V., Guerrini, R., Bisulli, F., Licchetta, L., Pippucci, T., Tinuper, P., Hirsch, E., Saint Martin, A. de, Chelly, J., Rudolf, G., Chipaux, M., Ferrand-Sorbets, S., Dorfmuller, G., Sisodiya, S., Balestrini, S., Schoeler, N., Hernandez-Hernandez, L., Krithika, S., Oegema, R., Hagebeuk, E., Gunning, B., Deckers, C., Berghuis, B., Wegner, I., Niks, E.H., Jansen, F.E., Braun, K., Jong, D. de, Rubboli, G., Talvik, I., Sander, V., Uldall, P., Jacquemont, M.L., Nava, C., Leguern, E., Julia, S., Gambardella, A., d'Orsi, G., Crichiutti, G., Faivre, L., Darmency, V., Benova, B., Krsek, P., Biraben, A., Lebre, A.S., Jennesson, M., Sattar, S., Marchal, C., Nordli, D.R., Lindstrom, K., Striano, P., Lomax, L.B., Kiss, C., Bartolomei, F., Lepine, A.F., Schoonjans, A.S., Stouffs, K., Jansen, A., Panagiotakaki, E., Ricard-Mousnier, B., Thevenon, J., Bellescize, J. de, Catenoix, H., Dorn, T., Zenker, M., Muller-Schluter, K., Brandt, C., Krey, I., Polster, T., Wolff, M., Balci, M., Rostasy, K., Achaz, G., Zacher, P., Becher, T., Cloppenborg, T., Yuskaitis, C.J., Weckhuysen, S., Poduri, A., Lemke, J.R., Moller, R.S., and Baulac, S.

Published
2019

23. SON haploinsufficiency causes impaired pre-mRNA splicing of CAKUT genes and heterogeneous renal phenotypes

Author

Kim, J.H., Park, E.Y., Chitayat, D., Stachura, D.L., Schaper, J., Lindstrom, K., Jewett, T., Wieczorek, D., Draaisma, J.M., Sinnema, M., Hoeberigs, C., Hempel, M., Bachman, K.K., Seeley, A.H., Stone, J.K., Kong, H.K., Vukadin, L., Richard, A., Shinde, D.N., McWalter, K., Si, Y.C., Douglas, G., Lim, S.T., Vissers, L.E.L.M., Lemaire, M., Ahn, E.E., Kim, J.H., Park, E.Y., Chitayat, D., Stachura, D.L., Schaper, J., Lindstrom, K., Jewett, T., Wieczorek, D., Draaisma, J.M., Sinnema, M., Hoeberigs, C., Hempel, M., Bachman, K.K., Seeley, A.H., Stone, J.K., Kong, H.K., Vukadin, L., Richard, A., Shinde, D.N., McWalter, K., Si, Y.C., Douglas, G., Lim, S.T., Vissers, L.E.L.M., Lemaire, M., and Ahn, E.E.

Abstract

Contains fulltext : 204239.pdf (Publisher’s version ) (Closed access), Although genetic testing is increasingly used in clinical nephrology, a large number of patients with congenital abnormalities of the kidney and urinary tract (CAKUT) remain undiagnosed with current gene panels. Therefore, careful curation of novel genetic findings is key to improving diagnostic yields. We recently described a novel intellectual disability syndrome caused by de novo heterozygous loss-of-function mutations in the gene encoding the splicing factor SON. Here, we show that many of these patients, including two previously unreported, exhibit a wide array of kidney abnormalities. Detailed phenotyping of 14 patients with SON haploinsufficiency identified kidney anomalies in 8 patients, including horseshoe kidney, unilateral renal hypoplasia, and renal cysts. Recurrent urinary tract infections, electrolyte disturbances, and hypertension were also observed in some patients. SON knockdown in kidney cell lines leads to abnormal pre-mRNA splicing, resulting in decreased expression of several established CAKUT genes. Furthermore, these molecular events were observed in patient-derived cells with SON haploinsufficiency. Taken together, our data suggest that the wide spectrum of phenotypes in patients with a pathogenic SON mutation is a consequence of impaired pre-mRNA splicing of several CAKUT genes. We propose that genetic testing panels designed to diagnose children with a kidney phenotype should include the SON gene.

Published
2019

24. De novo variants disruting the HX repeat motif of ATN1 cause a non-progressive neurocognitive disorder with recognisable facial features and congenital malformations

Author

Palmer, EE, Hong, S, Al Zahrani, F, Hashem, MO, Aleisa, FA, Ahmed, HMJ, Kandula, T, Macintosh, R, Minoche, A, Puttick, C, Gayevskiy, V, Drew, AP, Cowley, MJ, Dinger, ME, Rosenfeld, JA, Xiao, R, Cho, MT, Henderson, LB, Sacoto, MJG, Begtrup, A, Hamad, M, Shinawi, M, Andrews, M, Jones, MC, Lindstrom, K, Kayani, S, Snyder, M, Villanueva, M, Schteinschnaider, A, Roscioli, T, Kirk, EP, Bye, A, Merzaban, J, Jaremko, L, Jaremko, M, Sachdev, RK, Alkuraya, FS, Arold, ST, Palmer, EE, Hong, S, Al Zahrani, F, Hashem, MO, Aleisa, FA, Ahmed, HMJ, Kandula, T, Macintosh, R, Minoche, A, Puttick, C, Gayevskiy, V, Drew, AP, Cowley, MJ, Dinger, ME, Rosenfeld, JA, Xiao, R, Cho, MT, Henderson, LB, Sacoto, MJG, Begtrup, A, Hamad, M, Shinawi, M, Andrews, M, Jones, MC, Lindstrom, K, Kayani, S, Snyder, M, Villanueva, M, Schteinschnaider, A, Roscioli, T, Kirk, EP, Bye, A, Merzaban, J, Jaremko, L, Jaremko, M, Sachdev, RK, Alkuraya, FS, and Arold, ST

Published
2019

25. Erratum: De Novo Variants Disrupting the HX Repeat Motif of ATN1 Cause a Recognizable Non-progressive Neurocognitive Syndrome (The American Journal of Human Genetics (2019) 104(3) (542–552), (S0002929719300138), (10.1016/j.ajhg.2019.01.013))

Author

Palmer, EE, Hong, S, Al Zahrani, F, Hashem, MO, Aleisa, FA, Jalal Ahmed, HM, Kandula, T, Macintosh, R, Minoche, AE, Puttick, C, Gayevskiy, V, Drew, AP, Cowley, MJ, Dinger, M, Rosenfeld, JA, Xiao, R, Cho, MT, Yakubu, SF, Henderson, LB, Guillen Sacoto, MJ, Begtrup, A, Hamad, M, Shinawi, M, Andrews, MV, Jones, MC, Lindstrom, K, Bristol, RE, Kayani, S, Snyder, M, Villanueva, MM, Schteinschnaider, A, Faivre, L, Thauvin, C, Vitobello, A, Roscioli, T, Kirk, EP, Bye, A, Merzaban, J, Jaremko, Ł, Jaremko, M, Sachdev, RK, Alkuraya, FS, Arold, ST, Palmer, EE, Hong, S, Al Zahrani, F, Hashem, MO, Aleisa, FA, Jalal Ahmed, HM, Kandula, T, Macintosh, R, Minoche, AE, Puttick, C, Gayevskiy, V, Drew, AP, Cowley, MJ, Dinger, M, Rosenfeld, JA, Xiao, R, Cho, MT, Yakubu, SF, Henderson, LB, Guillen Sacoto, MJ, Begtrup, A, Hamad, M, Shinawi, M, Andrews, MV, Jones, MC, Lindstrom, K, Bristol, RE, Kayani, S, Snyder, M, Villanueva, MM, Schteinschnaider, A, Faivre, L, Thauvin, C, Vitobello, A, Roscioli, T, Kirk, EP, Bye, A, Merzaban, J, Jaremko, Ł, Jaremko, M, Sachdev, RK, Alkuraya, FS, and Arold, ST

Abstract

(The American Journal of Human Genetics 104, 542–552; March 7, 2019) In the original version of this article published on March 7, 2019, Łukasz Jaremko's name was unfortunately misspelled as Łukas Jaremko. It appears correctly here and online. The Journal and the authors apologize for this error.

Published
2019

26. De Novo Variants Disrupting the HX Repeat Motif of ATN1 Cause a Recognizable Non-Progressive Neurocognitive Syndrome

Author

Palmer, EE, Hong, S, Al Zahrani, F, Hashem, MO, Aleisa, FA, Ahmed, HMJ, Kandula, T, Macintosh, R, Minoche, AE, Puttick, C, Gayevskiy, V, Drew, AP, Cowley, MJ, Dinger, M, Rosenfeld, JA, Xiao, R, Cho, MT, Yakubu, SF, Henderson, LB, Guillen Sacoto, MJ, Begtrup, A, Hamad, M, Shinawi, M, Andrews, MV, Jones, MC, Lindstrom, K, Bristol, RE, Kayani, S, Snyder, M, Villanueva, MM, Schteinschnaider, A, Faivre, L, Thauvin, C, Vitobello, A, Roscioli, T, Kirk, EP, Bye, A, Merzaban, J, Jaremko, Ł, Jaremko, M, Sachdev, RK, Alkuraya, FS, Arold, ST, Palmer, EE, Hong, S, Al Zahrani, F, Hashem, MO, Aleisa, FA, Ahmed, HMJ, Kandula, T, Macintosh, R, Minoche, AE, Puttick, C, Gayevskiy, V, Drew, AP, Cowley, MJ, Dinger, M, Rosenfeld, JA, Xiao, R, Cho, MT, Yakubu, SF, Henderson, LB, Guillen Sacoto, MJ, Begtrup, A, Hamad, M, Shinawi, M, Andrews, MV, Jones, MC, Lindstrom, K, Bristol, RE, Kayani, S, Snyder, M, Villanueva, MM, Schteinschnaider, A, Faivre, L, Thauvin, C, Vitobello, A, Roscioli, T, Kirk, EP, Bye, A, Merzaban, J, Jaremko, Ł, Jaremko, M, Sachdev, RK, Alkuraya, FS, and Arold, ST

Abstract

Polyglutamine expansions in the transcriptional co-repressor Atrophin-1, encoded by ATN1, cause the neurodegenerative condition dentatorubral-pallidoluysian atrophy (DRPLA) via a proposed novel toxic gain of function. We present detailed phenotypic information on eight unrelated individuals who have de novo missense and insertion variants within a conserved 16-amino-acid “HX repeat” motif of ATN1. Each of the affected individuals has severe cognitive impairment and hypotonia, a recognizable facial gestalt, and variable congenital anomalies. However, they lack the progressive symptoms typical of DRPLA neurodegeneration. To distinguish this subset of affected individuals from the DRPLA diagnosis, we suggest using the term CHEDDA (congenital hypotonia, epilepsy, developmental delay, digit abnormalities) to classify the condition. CHEDDA-related variants alter the particular structural features of the HX repeat motif, suggesting that CHEDDA results from perturbation of the structural and functional integrity of the HX repeat. We found several non-homologous human genes containing similar motifs of eight to 10 HX repeat sequences, including RERE, where disruptive variants in this motif have also been linked to a separate condition that causes neurocognitive and congenital anomalies. These findings suggest that perturbation of the HX motif might explain other Mendelian human conditions.

Published
2019

27. De novo truncating variants in the intronless IRF2BPL are responsible for developmental epileptic encephalopathy

Author

Genetica, Genetica Klinische Genetica, Child Health, Brain, ZL Kinder Ner en Nec Medisch, Genetica Sectie Genoomdiagnostiek, Tran Mau-Them, F., Guibaud, L., Duplomb, L., Keren, B., Lindstrom, K., Marey, I., Mochel, F., van den Boogaard, M. J., Oegema, R., Nava, C., Masurel, A., Jouan, T., Jansen, F. E., Au, M., Chen, Agnes H., Cho, M., Duffourd, Y., Lozier, E., Konovalov, F., Sharkov, A., Korostelev, S., Urteaga, B., Dickson, P., Vera, M., Martínez-Agosto, Julián A., Begemann, A., Zweier, M., Schmitt-Mechelke, T., Rauch, A., Philippe, C., van Gassen, K., Nelson, S., Graham, J. M., Friedman, J., Faivre, L., Lin, H. J., Thauvin-Robinet, C., Vitobello, A., Genetica, Genetica Klinische Genetica, Child Health, Brain, ZL Kinder Ner en Nec Medisch, Genetica Sectie Genoomdiagnostiek, Tran Mau-Them, F., Guibaud, L., Duplomb, L., Keren, B., Lindstrom, K., Marey, I., Mochel, F., van den Boogaard, M. J., Oegema, R., Nava, C., Masurel, A., Jouan, T., Jansen, F. E., Au, M., Chen, Agnes H., Cho, M., Duffourd, Y., Lozier, E., Konovalov, F., Sharkov, A., Korostelev, S., Urteaga, B., Dickson, P., Vera, M., Martínez-Agosto, Julián A., Begemann, A., Zweier, M., Schmitt-Mechelke, T., Rauch, A., Philippe, C., van Gassen, K., Nelson, S., Graham, J. M., Friedman, J., Faivre, L., Lin, H. J., Thauvin-Robinet, C., and Vitobello, A.

Published
2019

38. Previously undiagnosed attention-deficit/hyperactivity disorder associated with poor metabolic control in adolescents with type 1 diabetes

Author

Nylander, Charlotte, Lindstrom, K., Khalifa, Najah, Fernell, E., Nylander, Charlotte, Lindstrom, K., Khalifa, Najah, and Fernell, E.

Abstract

Background: Managing modern diabetes treatment requires efficient executive functions. Patients with attention-deficit/hyperactivity disorder (ADHD) and type 1 diabetes have poor metabolic control and present with ketoacidosis more often than patients without ADHD. Objective: To assess whether patients with type 1 diabetes and with indications of executive problems met criteria for ADHD, and to investigate whether these patients had difficulties achieving metabolic control. Methods: In a hospital-based study, including 3 pediatric departments at hospitals in Stockholm and Uppsala, Sweden, questionnaires regarding executive problems had been filled out by 12- to 18-year-old patients with type 1 diabetes and their parents. Out of 166 patients with completed questionnaires, 49 were selected for a clinical study due to reported executive problems/ADHD symptoms. However, 7 already had a diagnosis of ADHD, 21 denied follow-up, 8 did not respond, leaving 13 adolescents for the clinical assessment. Results: Of the clinically assessed adolescents, 9 (6 girls) met criteria for ADHD. Patients who did not respond to the follow-up and patients who were diagnosed with ADHD within the study, showed to a larger extent than the other study groups high HbA1c levels (>70 mmol/mol, 8,6%). HbA1c >70 mmol/mol (8.6%) was associated with diagnosed ADHD (prior to or within the study), odds ratio 2.96 (95% confidence interval 1.02-8.60). Conclusion: Patients with type 1 diabetes and poor metabolic control should be assessed with regard to ADHD. There is a need for paying special attention to girls with poor metabolic control.

Published
2018
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39. De Novo Pathogenic Variants in CACNA1E Cause Developmental and Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesias

Author

Helbig, K.L., Lauerer, R.J., Bahr, J.C., Souza, I.A., Myers, C.T., Uysal, B., Schwarz, N., Gandini, M.A., Huang, S., Keren, B., Mignot, C., Afenjar, A., Villemeur, T. Billette de, Heron, D., Nava, C., Valence, S., Buratti, J., Fagerberg, C.R., Soerensen, K.P., Kibaek, M., Kamsteeg, E.J., Koolen, D.A., Gunning, B., Schelhaas, H.J., Kruer, M.C., Fox, J., Bakhtiari, S., Jarrar, R., Padilla-Lopez, S., Lindstrom, K., Jin, S.C., Zeng, X., Bilguvar, K., Papavasileiou, A., Xin, Q., Zhu, C., Boysen, K., Vairo, F., Lanpher, B.C., Klee, E.W., Tillema, J.M., Payne, E.T., Cousin, M.A., Kruisselbrink, T.M., Wick, M.J., Baker, J., Haan, E., Smith, N., Corbett, M.A., MacLennan, A.H., Gecz, J., Biskup, S., Goldmann, E., Rodan, L.H., Kichula, E., Segal, E., Jackson, K.E., Asamoah, A., Dimmock, D., McCarrier, J., Botto, L.D., Filloux, F., Tvrdik, T., Cascino, G.D., Klingerman, S., Neumann, C., Wang, R., Jacobsen, J.C., Nolan, M.A., Snell, R.G., Lehnert, K., Sadleir, L.G., Anderlid, B.M., Kvarnung, M., Guerrini, R., Friez, M.J., Lyons, M.J., Leonhard, J., Kringlen, G., Casas, K., Achkar, C.M. El, Smith, L.A., Rotenberg, A., Poduri, A., Sanchis-Juan, A., Carss, K.J., Rankin, J., Zeman, A., Raymond, F.L., Blyth, M., Kerr, B., Ruiz, K., Urquhart, J., Hughes, I., Banka, S., Hedrich, U.B.S., Scheffer, I.E., Helbig, I., Zamponi, G.W., Lerche, H., et al., Helbig, K.L., Lauerer, R.J., Bahr, J.C., Souza, I.A., Myers, C.T., Uysal, B., Schwarz, N., Gandini, M.A., Huang, S., Keren, B., Mignot, C., Afenjar, A., Villemeur, T. Billette de, Heron, D., Nava, C., Valence, S., Buratti, J., Fagerberg, C.R., Soerensen, K.P., Kibaek, M., Kamsteeg, E.J., Koolen, D.A., Gunning, B., Schelhaas, H.J., Kruer, M.C., Fox, J., Bakhtiari, S., Jarrar, R., Padilla-Lopez, S., Lindstrom, K., Jin, S.C., Zeng, X., Bilguvar, K., Papavasileiou, A., Xin, Q., Zhu, C., Boysen, K., Vairo, F., Lanpher, B.C., Klee, E.W., Tillema, J.M., Payne, E.T., Cousin, M.A., Kruisselbrink, T.M., Wick, M.J., Baker, J., Haan, E., Smith, N., Corbett, M.A., MacLennan, A.H., Gecz, J., Biskup, S., Goldmann, E., Rodan, L.H., Kichula, E., Segal, E., Jackson, K.E., Asamoah, A., Dimmock, D., McCarrier, J., Botto, L.D., Filloux, F., Tvrdik, T., Cascino, G.D., Klingerman, S., Neumann, C., Wang, R., Jacobsen, J.C., Nolan, M.A., Snell, R.G., Lehnert, K., Sadleir, L.G., Anderlid, B.M., Kvarnung, M., Guerrini, R., Friez, M.J., Lyons, M.J., Leonhard, J., Kringlen, G., Casas, K., Achkar, C.M. El, Smith, L.A., Rotenberg, A., Poduri, A., Sanchis-Juan, A., Carss, K.J., Rankin, J., Zeman, A., Raymond, F.L., Blyth, M., Kerr, B., Ruiz, K., Urquhart, J., Hughes, I., Banka, S., Hedrich, U.B.S., Scheffer, I.E., Helbig, I., Zamponi, G.W., and Lerche, H., et al.

Abstract

Item does not contain fulltext, Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that are characterized by intractable seizures, abundant epileptiform activity on EEG, and developmental impairment or regression. CACNA1E is highly expressed in the central nervous system and encodes the alpha1-subunit of the voltage-gated CaV2.3 channel, which conducts high voltage-activated R-type calcium currents that initiate synaptic transmission. Using next-generation sequencing techniques, we identified de novo CACNA1E variants in 30 individuals with DEE, characterized by refractory infantile-onset seizures, severe hypotonia, and profound developmental impairment, often with congenital contractures, macrocephaly, hyperkinetic movement disorders, and early death. Most of the 14, partially recurring, variants cluster within the cytoplasmic ends of all four S6 segments, which form the presumed CaV2.3 channel activation gate. Functional analysis of several S6 variants revealed consistent gain-of-function effects comprising facilitated voltage-dependent activation and slowed inactivation. Another variant located in the domain II S4-S5 linker results in facilitated activation and increased current density. Five participants achieved seizure freedom on the anti-epileptic drug topiramate, which blocks R-type calcium channels. We establish pathogenic variants in CACNA1E as a cause of DEEs and suggest facilitated R-type calcium currents as a disease mechanism for human epilepsy and developmental disorders.

Published
2018

40. Regional differences in milk and complementary feeding patterns in infants participating in an international nutritional type 1 diabetes prevention trial

Author

Nucci, A. M., Virtanen, S. M., Sorkio, S., Barlund, S., Cuthbertson, D., Uusitalo, U., Lawson, M. L., Salonen, M., Berseth, C. L., Ormisson, A., Lehtonen, E., Savilahti, E., Becker, D. J., Dupre, J., Krischer, J. P., Knip, M., Akerblom, H. K., Mandrup-Poulsen, T., Arjas, E., Laara, E., Lernmark, A., Schmidt, B., Hyytinen, M., Koski, K., Koski, M., Pajakkala, E., Shanker, L., Bradley, B., Dosch, H. -M., Fraser, W., Lawson, M., Mahon, J. L., Sermer, M., Taback, S. P., Becker, D., Franciscus, M., Nucci, A., Palmer, J., Pekkala, M., Catteau, J., Howard, N., Crock, P., Craig, M., Clarson, C. L., Bere, L., Thompson, D., Metzger, D., Kwan, J., Stephure, D. K., Pacaud, D., Ho, J., Schwarz, W., Girgis, R., Thompson, M., Catte, D., Daneman, D., Martin, M. -J., Morin, V., Frenette, L., Ferland, S., Sanderson, S., Heath, K., Huot, C., Gonthier, M., Thibeault, M., Legault, L., Laforte, D., Cummings, E. A., Scott, K., Bridger, T., Crummell, C., Newman, S., Houlden, R., Breen, A., Carson, G., Kelly, S., Sankaran, K., Penner, M., White, R. A., Hardy Brown, K., King, N., Popkin, J., Robson, L., Coles, K., Al Taji, E., Aldhoon, I., Mendlova, P., Vavrinec, J., Vosahlo, J., Brazdova, L., Venhacova, J., Venhacova, P., Cipra, A., Tomsikova, Z., Paterova, P., Gogelova, P., Einberg, U., Riikjarv, M. -A., Tillmann, V., Hirvasniemi, M., Kleemola, P., Parkkola, A., Suomalainen, H., Jarvenpaa, A. -L., Hamalainen, A. -M., Haavisto, H., Tenhola, S., Lautala, P., Salonen, P., Aspholm, S., Siljander, H., Holm, C., Ylitalo, S., Lounamaa, R., Nuuja, A., Talvitie, T., Lindstrom, K., Huopio, H., Pesola, J., Veijola, R., Tapanainen, P., Alar, A., Korpela, P., Kaar, M. -L., Mustila, T., Virransalo, R., Nykanen, P., Aschemeier, B., Danne, T., Kordonouri, O., Krikovszky, D., Madacsy, L., Khazrai, Y. M., Maddaloni, E., Pozzilli, P., Mannu, C., Songini, M., de Beaufort, C., Schierloh, U., Bruining, J., Basiak, A., Wasikowa, R., Ciechanowska, M., Deja, G., Jarosz-Chobot, P., Szadkowska, A., Cypryk, K., Zawodniak-Szalapska, M., Castano, L., Gonzalez Frutos, T., Oyarzabal, M., Serrano-Rios, M., Martinez-Larrad, M. T., Hawkins, F. G., Rodriguez Arnau, D., Ludvigsson, J., Smolinska Konefal, M., Hanas, R., Lindblad, B., Nilsson, N. -O., Fors, H., Nordwall, M., Lindh, A., Edenwall, H., Aman, J., Johansson, C., Gadient, M., Schoenle, E., Daftary, A., Klein, M. B., Gilmour, C., Malone, P., Tanner-Blasiar, M., White, N., Devaskar, U., Horowitz, H., Rogers, L., Colon, R., Frazer, T., Torres, J., Goland, R., Greenberg, E., Nelson, M., Schachner, H., Softness, B., Ilonen, J., Trucco, M., Nichol, L., Harkonen, T., Vaarala, O., and Luopajarvi, K.

Subjects
Canada, endocrine system diseases, infant feeding, breastfeeding, type 1 diabetes, breastfeeding duration, complementary feeding, infant formula, Infant, Article, United States, Diet, Nutrition Policy, Europe, Diabetes Mellitus, Type 1, Milk, Nutrition Assessment, Double-Blind Method, Surveys and Questionnaires, Animals, Humans, Infant Food, Prospective Studies, Infant Nutritional Physiological Phenomena
Abstract

Differences in breastfeeding, other milk feeding and complementary feeding patterns were evaluated in infants at increased genetic risk with and without maternal type 1 diabetes (T1D). The Trial to Reduce IDDM in the Genetically at Risk is an international nutritional primary prevention double-blinded randomized trial to test whether weaning to extensively hydrolyzed vs. intact cow's milk protein formula will decrease the development of T1D-associated autoantibodies and T1D. Infant diet was prospectively assessed at two visits and seven telephone interviews between birth and 8 months. Countries were grouped into seven regions: Australia, Canada, Northern Europe, Southern Europe, Central Europe I, Central Europe II and the United States. Newborn infants with a first-degree relative with T1D and increased human leukocyte antigen-conferred susceptibility to T1D were recruited. A lower proportion of infants born to mothers with than without T1D were breastfed until 6 months of age in all regions (range, 51% to 60% vs. 70% to 80%). Complementary feeding patterns differed more by region than by maternal T1D. In Northern Europe, a higher proportion of infants consumed vegetables and fruits daily compared with other regions. Consumption of meat was more frequent in all European regions, whereas cereal consumption was most frequent in Southern Europe, Canada and the United States. Maternal T1D status was associated with breastfeeding and other milk feeding patterns similarly across regions but was unrelated to the introduction of complementary foods. Infant feeding patterns differed significantly among regions and were largely inconsistent with current recommended guidelines.

Published
2017

41. Novel group within the kingdom Crenarchaeota from boreal forest soil

Author

Jurgens, G., Lindstrom, K., and Saano, A.

Subjects
Forest soils -- Analysis, Soil microbiology -- Observations, Ribosomal RNA -- Observations, Nucleotide sequence -- Analysis, Phylogeny -- Observations, Biological sciences
Abstract

Nucleotide sequence and phylogenetic analyses reveals that the archaeal 16S rRNA sequences from forest soil belong to the domain Archaea and form a new cluster. The phylogenetic position of this cluster suggests that the sequences belong to the terrestrial low-temperature Crenarchaeota kingdom. PCR amplification techniques along with Archaea-specific primers containing mixed-population DNA help to analyse the gene sequence.

Published
1997

43. Divergent genes in potential inoculant Sinorhizobium strains are related to DNA replication, recombination, and repair

Author

Penttinen, P., Greco, D., Muntyan, V., Terefework, Z., Lajudie, Philippe de, Roumiantseva, M., Becker, A., Auvinen, P., and Lindstrom, K.

Subjects
bacteria, food and beverages, Comparative genomic hybridisation, Agricultural inoculants, biochemical phenomena, metabolism, and nutrition, Symbiosis
Abstract

To serve as inoculants of legumes, nitrogen-fixing rhizobium strains should be competitive and tolerant of diverse environments. We hybridized the genomes of symbiotically efficient and salt tolerant Sinorhizobium inoculant strains onto the Sinorhizobium meliloti Rm1021 microarray. The number of variable genes, that is, divergent or putatively multiplied genes, ranged from 503 to 1556 for S. meliloti AK23, S. meliloti STM 1064 and S. arboris HAMBI 1552. The numbers of divergent genes affiliated with the symbiosis plasmid pSymA and related to DNA replication, recombination and repair were significantly higher than expected. The variation was mainly in the accessory genome, implying that it was important in shaping the adaptability of the strains.

Published
2016

46. Symbiotic and genetic diversity of Rhizobium galegae isolates collected from the Galega orientalis gene center in the Caucasus

Author

Andronov, E. E., Terefework, Z., Roumiantseva, M. L., Dzyubenko, N. I., Onichtchouk, O. P., Kurchak, O.N., Dresler-Nurmi, A., Young, J. P. W., Simarov, B. V., and Lindstrom, K.

Subjects
Rhizobium -- Genetic aspects, Symbiosis -- Genetic aspects, Biological diversity -- Genetic aspects, Genomes -- Comparative analysis, Biological sciences
Abstract

Results indicate an evolutionary pressure on the symbiotic genome of Rhizobium galegae biovars as seen in the formation of distinct clusters by the R. galegae biovar officinalis and R. galegae biovar orientalis. Further, the Caucasian R. galegae biovar orientalis strains exhibit more diversity than R. galegae biovar officinalis strains.

Published
2003

47. De Novo Mutations in SON Disrupt RNA Splicing of Genes Essential for Brain Development and Metabolism, Causing an Intellectual-Disability Syndrome

Author

Kim, J.H., Shinde, D.N., Reijnders, M.R.F., Hauser, N.S., Belmonte, R.L., Wilson, G.R., Bosch, D.G.M., Bubulya, P.A., Shashi, V., Petrovski, S., Stone, J.K., Park, E.Y., Veltman, J.A., Sinnema, M., Stumpel, C.T., Draaisma, J.M., Nicolai, J., Yntema, H.G., Lindstrom, K., Vries, B.B. de, Jewett, T., Santoro, S.L., Vogt, J., Bachman, K.K., Seeley, A.H., Krokosky, A., Turner, C., Rohena, L., Hempel, M., Kortum, F., Lessel, D., Neu, A., Strom, T.M., Wieczorek, D., Bramswig, N., Laccone, F.A., Behunova, J., Rehder, H., Gordon, C.T., Rio, M. del, Romana, S., Tang, S., El-Khechen, D., Cho, M.T., McWalter, K., Douglas, G., Baskin, B., Begtrup, A., Funari, T., Schoch, K., Stegmann, A.P., Stevens, S.J., Zhang, D.E., Traver, D., Yao, X., MacArthur, D.G., Brunner, H.G., Mancini, G.M., Myers, R.M., Owen, L.B., Lim, S.T., Stachura, D.L., Vissers, L.E.L.M., Ahn, E.Y., Kim, J.H., Shinde, D.N., Reijnders, M.R.F., Hauser, N.S., Belmonte, R.L., Wilson, G.R., Bosch, D.G.M., Bubulya, P.A., Shashi, V., Petrovski, S., Stone, J.K., Park, E.Y., Veltman, J.A., Sinnema, M., Stumpel, C.T., Draaisma, J.M., Nicolai, J., Yntema, H.G., Lindstrom, K., Vries, B.B. de, Jewett, T., Santoro, S.L., Vogt, J., Bachman, K.K., Seeley, A.H., Krokosky, A., Turner, C., Rohena, L., Hempel, M., Kortum, F., Lessel, D., Neu, A., Strom, T.M., Wieczorek, D., Bramswig, N., Laccone, F.A., Behunova, J., Rehder, H., Gordon, C.T., Rio, M. del, Romana, S., Tang, S., El-Khechen, D., Cho, M.T., McWalter, K., Douglas, G., Baskin, B., Begtrup, A., Funari, T., Schoch, K., Stegmann, A.P., Stevens, S.J., Zhang, D.E., Traver, D., Yao, X., MacArthur, D.G., Brunner, H.G., Mancini, G.M., Myers, R.M., Owen, L.B., Lim, S.T., Stachura, D.L., Vissers, L.E.L.M., and Ahn, E.Y.

Abstract

Item does not contain fulltext, The overall understanding of the molecular etiologies of intellectual disability (ID) and developmental delay (DD) is increasing as next-generation sequencing technologies identify genetic variants in individuals with such disorders. However, detailed analyses conclusively confirming these variants, as well as the underlying molecular mechanisms explaining the diseases, are often lacking. Here, we report on an ID syndrome caused by de novo heterozygous loss-of-function (LoF) mutations in SON. The syndrome is characterized by ID and/or DD, malformations of the cerebral cortex, epilepsy, vision problems, musculoskeletal abnormalities, and congenital malformations. Knockdown of son in zebrafish resulted in severe malformation of the spine, brain, and eyes. Importantly, analyses of RNA from affected individuals revealed that genes critical for neuronal migration and cortex organization (TUBG1, FLNA, PNKP, WDR62, PSMD3, and HDAC6) and metabolism (PCK2, PFKL, IDH2, ACY1, and ADA) are significantly downregulated because of the accumulation of mis-spliced transcripts resulting from erroneous SON-mediated RNA splicing. Our data highlight SON as a master regulator governing neurodevelopment and demonstrate the importance of SON-mediated RNA splicing in human development.

Published
2016

48. De Novo Mutations of RERE Cause a Genetic Syndrome with Features that Overlap Those Associated with Proximal 1p36 Deletions

Author

Fregeau, B., Kim, B.J., Hernandez-Garcia, A., Jordan, V.K., Cho, M.T., Schnur, R.E., Monaghan, K.G., Juusola, J., Rosenfeld, J.A., Bhoj, E., Zackai, E.H., Sacharow, S., Baranano, K., Bosch, D.G.M., Vries, B.B.A. de, Lindstrom, K., Schroeder, A., James, P., Kulch, P., Lalani, S.R., Haelst, M.M. van, Gassen, K.L. van, Binsbergen, E. van, Barkovich, A.J., Scott, D.A., Sherr, E.H., Fregeau, B., Kim, B.J., Hernandez-Garcia, A., Jordan, V.K., Cho, M.T., Schnur, R.E., Monaghan, K.G., Juusola, J., Rosenfeld, J.A., Bhoj, E., Zackai, E.H., Sacharow, S., Baranano, K., Bosch, D.G.M., Vries, B.B.A. de, Lindstrom, K., Schroeder, A., James, P., Kulch, P., Lalani, S.R., Haelst, M.M. van, Gassen, K.L. van, Binsbergen, E. van, Barkovich, A.J., Scott, D.A., and Sherr, E.H.

Abstract

Item does not contain fulltext, Deletions of chromosome 1p36 affect approximately 1 in 5,000 newborns and are associated with developmental delay, intellectual disability, and defects involving the brain, eye, ear, heart, and kidney. Arginine-glutamic acid dipeptide repeats (RERE) is located in the proximal 1p36 critical region. RERE is a widely-expressed nuclear receptor coregulator that positively regulates retinoic acid signaling. Animal models suggest that RERE deficiency might contribute to many of the structural and developmental birth defects and medical problems seen in individuals with 1p36 deletion syndrome, although human evidence supporting this role has been lacking. In this report, we describe ten individuals with intellectual disability, developmental delay, and/or autism spectrum disorder who carry rare and putatively damaging changes in RERE. In all cases in which both parental DNA samples were available, these changes were found to be de novo. Associated features that were recurrently seen in these individuals included hypotonia, seizures, behavioral problems, structural CNS anomalies, ophthalmologic anomalies, congenital heart defects, and genitourinary abnormalities. The spectrum of defects documented in these individuals is similar to that of a cohort of 31 individuals with isolated 1p36 deletions that include RERE and are recapitulated in RERE-deficient zebrafish and mice. Taken together, our findings suggest that mutations in RERE cause a genetic syndrome and that haploinsufficiency of RERE might be sufficient to cause many of the phenotypes associated with proximal 1p36 deletions.

Published
2016

49. De Novo Mutations in SON Disrupt RNA Splicing of Genes Essential for Brain Development and Metabolism, Causing an Intellectual-Disability Syndrome

Author

Kim, J.-H. (Jung-Hyun), Shinde, D.N. (Deepali N.), Reijnders, M.R.F. (Margot R.F.), Hauser, N.S. (Natalie S.), Belmonte, R.L. (Rebecca L.), Wilson, G.R. (Gregory R.), Bosch, D.G.M. (Daniëlle G.M.), Bubulya, P.A. (Paula A.), Shashi, V. (Vandana), Petrovski, S. (Slavé), Stone, J.K. (Joshua K.), Park, E.Y. (Eun Young), Veltman, J.A. (Joris), Sinnema, M. (Margje), Stumpel, C. (Connie), Draaisma, J. (Jos), Nicolai, J. (Joost), Yntema, H.G., Lindstrom, K. (Kristin), Vries, B. (Boukje) de, Jewett, T. (Tamison), Santoro, S.L. (Stephanie L.), Vogt, J. (Julie), Bachman, K.K. (Kristine K.), Seeley, A.H. (Andrea ), Krokosky, A. (Alyson), Turner, C. (Clesson), Rohena, L. (Luis), Hempel, M. (Maja), Kortüm, F. (Fanny), Lessel, D. (Davor), Neu, A. (Axel), Strom, T.M. (Tim), Wieczorek, D. (Dagmar), Bramswig, N. (Nuria), Laccone, F.A. (Franco A.), Behunova, J. (Jana), Rehder, H. (Helga), Gordon, C.T. (Christopher T.), Rio, M. (Marlène), Romana, S. (Serge), Tang, S. (Sha), El-Khechen, D. (Dima), Cho, M.T. (Megan T.), McWalter, K. (Kirsty), Douglas, G. (Ganka), Baskin, B. (Berivan), Begtrup, A. (Amber), Funari, T. (Tara), Schoch, K. (Kelly), Stegmann, A.P.A. (Alexander P.A.), Stevens, S.J., Zhang, D.-E. (Dong-Er), Traver, D. (David), Yao, X. (Xu), MacArthur, D.G. (Daniel G.), Brunner, H.G., Mancini, G.M.S. (Grazia), Myers, R.H. (Richard), Owen, L.B. (Laurie B.), Lim, S.-T. (Ssang-Taek), Stachura, D.L. (David L.), Vissers, L.E.L.M., Ahn, E.-Y.E. (Eun-Young Erin), Kim, J.-H. (Jung-Hyun), Shinde, D.N. (Deepali N.), Reijnders, M.R.F. (Margot R.F.), Hauser, N.S. (Natalie S.), Belmonte, R.L. (Rebecca L.), Wilson, G.R. (Gregory R.), Bosch, D.G.M. (Daniëlle G.M.), Bubulya, P.A. (Paula A.), Shashi, V. (Vandana), Petrovski, S. (Slavé), Stone, J.K. (Joshua K.), Park, E.Y. (Eun Young), Veltman, J.A. (Joris), Sinnema, M. (Margje), Stumpel, C. (Connie), Draaisma, J. (Jos), Nicolai, J. (Joost), Yntema, H.G., Lindstrom, K. (Kristin), Vries, B. (Boukje) de, Jewett, T. (Tamison), Santoro, S.L. (Stephanie L.), Vogt, J. (Julie), Bachman, K.K. (Kristine K.), Seeley, A.H. (Andrea ), Krokosky, A. (Alyson), Turner, C. (Clesson), Rohena, L. (Luis), Hempel, M. (Maja), Kortüm, F. (Fanny), Lessel, D. (Davor), Neu, A. (Axel), Strom, T.M. (Tim), Wieczorek, D. (Dagmar), Bramswig, N. (Nuria), Laccone, F.A. (Franco A.), Behunova, J. (Jana), Rehder, H. (Helga), Gordon, C.T. (Christopher T.), Rio, M. (Marlène), Romana, S. (Serge), Tang, S. (Sha), El-Khechen, D. (Dima), Cho, M.T. (Megan T.), McWalter, K. (Kirsty), Douglas, G. (Ganka), Baskin, B. (Berivan), Begtrup, A. (Amber), Funari, T. (Tara), Schoch, K. (Kelly), Stegmann, A.P.A. (Alexander P.A.), Stevens, S.J., Zhang, D.-E. (Dong-Er), Traver, D. (David), Yao, X. (Xu), MacArthur, D.G. (Daniel G.), Brunner, H.G., Mancini, G.M.S. (Grazia), Myers, R.H. (Richard), Owen, L.B. (Laurie B.), Lim, S.-T. (Ssang-Taek), Stachura, D.L. (David L.), Vissers, L.E.L.M., and Ahn, E.-Y.E. (Eun-Young Erin)

Abstract

The overall understanding of the molecular etiologies of intellectual disability (ID) and developmental delay (DD) is increasing as next-generation sequencing technologies identify genetic variants in individuals with such disorders. However, detailed analyses c

Published
2016
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