Search

Your search keyword '"Roifman, Maian"' showing total 40 results
Start Over Author "Roifman, Maian"
40 results on '"Roifman, Maian"'

1. Expanding the phenotypic spectrum of NOTCH1 variants: clinical manifestations in families with congenital heart disease

Author

Stanley, Kaitlin J., Kalbfleisch, Kelsey J., Moran, Olivia M., Chaturvedi, Rajiv R., Roifman, Maian, Chen, Xin, Manshaei, Roozbeh, Martin, Nicole, McDermott, Simina, McNiven, Vanda, Myles-Reid, Diane, Nield, Lynne E., Reuter, Miriam S., Schwartz, Marci L. B., Shannon, Patrick, Silver, Rachel, Somerville, Cherith, Teitelbaum, Ronni, Zahavich, Laura, Bassett, Anne S., Kim, Raymond H., Mital, Seema, Chitayat, David, and Jobling, Rebekah K.

Published
2024
Full Text
View/download PDF

2. Pathogenic variants in KMT2C result in a neurodevelopmental disorder distinct from Kleefstra and Kabuki syndromes

Author

Rots, Dmitrijs, Choufani, Sanaa, Faundes, Victor, Dingemans, Alexander J.M., Joss, Shelagh, Foulds, Nicola, Jones, Elizabeth A., Stewart, Sarah, Vasudevan, Pradeep, Dabir, Tabib, Park, Soo-Mi, Jewell, Rosalyn, Brown, Natasha, Pais, Lynn, Jacquemont, Sébastien, Jizi, Khadijé, Ravenswaaij-Arts, Conny M.A. van, Kroes, Hester Y., Stumpel, Constance T.R. M., Ockeloen, Charlotte W., Diets, Illja J., Nizon, Mathilde, Vincent, Marie, Cogné, Benjamin, Besnard, Thomas, Kambouris, Marios, Anderson, Emily, Zackai, Elaine H., McDougall, Carey, Donoghue, Sarah, O'Donnell-Luria, Anne, Valivullah, Zaheer, O'Leary, Melanie, Srivastava, Siddharth, Byers, Heather, Leslie, Nancy, Mazzola, Sarah, Tiller, George E., Vera, Moin, Shen, Joseph J., Boles, Richard, Jain, Vani, Brischoux-Boucher, Elise, Kinning, Esther, Simpson, Brittany N., Giltay, Jacques C., Harris, Jacqueline, Keren, Boris, Guimier, Anne, Marijon, Pierre, Vries, Bert B.A. de, Motter, Constance S., Mendelsohn, Bryce A., Coffino, Samantha, Gerkes, Erica H., Afenjar, Alexandra, Visconti, Paola, Bacchelli, Elena, Maestrini, Elena, Delahaye-Duriez, Andree, Gooch, Catherine, Hendriks, Yvonne, Adams, Hieab, Thauvin-Robinet, Christel, Josephi-Taylor, Sarah, Bertoli, Marta, Parker, Michael J., Rutten, Julie W., Caluseriu, Oana, Vernon, Hilary J., Kaziyev, Jonah, Zhu, Jia, Kremen, Jessica, Frazier, Zoe, Osika, Hailey, Breault, David, Nair, Sreelata, Lewis, Suzanne M.E., Ceroni, Fabiola, Viggiano, Marta, Posar, Annio, Brittain, Helen, Giovanna, Traficante, Giulia, Gori, Quteineh, Lina, Ha-Vinh Leuchter, Russia, Zonneveld-Huijssoon, Evelien, Mellado, Cecilia, Marey, Isabelle, Coudert, Alicia, Aracena Alvarez, Mariana Inés, Kennis, Milou G.P., Bouman, Arianne, Roifman, Maian, Amorós Rodríguez, María Inmaculada, Ortigoza-Escobar, Juan Dario, Vernimmen, Vivian, Sinnema, Margje, Pfundt, Rolph, Brunner, Han G., Vissers, Lisenka E.L.M., Kleefstra, Tjitske, Weksberg, Rosanna, and Banka, Siddharth

Published
2024
Full Text
View/download PDF

5. Loss-of-Function Variants in PPP1R12A: From Isolated Sex Reversal to Holoprosencephaly Spectrum and Urogenital Malformations.

Author

Hughes, Joel, Alkhunaizi, Ebba, Kruszka, Paul, Pyle, Louise, Grange, Dorothy, Berger, Seth, Payne, Katelyn, Masser-Frye, Diane, Hu, Tommy, Christie, Michelle, Clegg, Nancy, Everson, Joshua, Martinez, Ariel, Walsh, Laurence, Bedoukian, Emma, Jones, Marilyn, Harris, Catharine, Riedhammer, Korbinian, Choukair, Daniela, Fechner, Patricia, Rutter, Meilan, Hufnagel, Sophia, Roifman, Maian, Kletter, Gad, Delot, Emmanuele, Vilain, Eric, Lipinski, Robert, Vezina, Chad, Muenke, Maximilian, and Chitayat, David

Subjects
MYPT1, PPP1R12A, disorders of sex development, embryogenesis, encephalocele, facial dysmorphism, forebrain, holoprosencephaly, hypospadias, omphalocele, Abnormalities, Multiple, Adolescent, Child, Child, Preschool, Disorders of Sex Development, Female, Gestational Age, Holoprosencephaly, Humans, Male, Mutation, Myosin-Light-Chain Phosphatase, Phenotype, Pregnancy, Urogenital Abnormalities
Abstract

In two independent ongoing next-generation sequencing projects for individuals with holoprosencephaly and individuals with disorders of sex development, and through international research collaboration, we identified twelve individuals with de novo loss-of-function (LoF) variants in protein phosphatase 1, regulatory subunit 12a (PPP1R12A), an important developmental gene involved in cell migration, adhesion, and morphogenesis. This gene has not been previously reported in association with human disease, and it has intolerance to LoF as illustrated by a very low observed-to-expected ratio of LoF variants in gnomAD. Of the twelve individuals, midline brain malformations were found in five, urogenital anomalies in nine, and a combination of both phenotypes in two. Other congenital anomalies identified included omphalocele, jejunal, and ileal atresia with aberrant mesenteric blood supply, and syndactyly. Six individuals had stop gain variants, five had a deletion or duplication resulting in a frameshift, and one had a canonical splice acceptor site loss. Murine and human in situ hybridization and immunostaining revealed PPP1R12A expression in the prosencephalic neural folds and protein localization in the lower urinary tract at critical periods for forebrain division and urogenital development. Based on these clinical and molecular findings, we propose the association of PPP1R12A pathogenic variants with a congenital malformations syndrome affecting the embryogenesis of the brain and genitourinary systems and including disorders of sex development.

Published
2020

7. Expanding the phenotypic spectrum of NOTCH1 variants: Clinical manifestations in families with congenital heart disease

Author

Jobling, Rebekah, primary, Stanley, Kaitlin, additional, Kalbfleisch, Kelsey, additional, Moran, Olivia, additional, Chaturvedi, Rajiv, additional, Roifman, Maian, additional, Manshaei, Roozbeh, additional, Martin, Nicole, additional, McDermott, Simina, additional, McNiven, Vanda, additional, Myles-Reid, Diane, additional, Nield, Lynne, additional, Reuter, Miriam, additional, Schwartz, Marci, additional, Shannon, Patrick, additional, Silver, Rachel, additional, Somerville, Cherith, additional, Teitelbaum, Ronni, additional, Zahavich, Laura, additional, Bassett, Anne, additional, Kim, Raymond, additional, Mital, Seema, additional, and Chitayat, David, additional

Published
2024
Full Text
View/download PDF

8. Expanding the phenotypic spectrum of NOTCH1variants: clinical manifestations in families with congenital heart disease

Author

Stanley, Kaitlin J., Kalbfleisch, Kelsey J., Moran, Olivia M., Chaturvedi, Rajiv R., Roifman, Maian, Chen, Xin, Manshaei, Roozbeh, Martin, Nicole, McDermott, Simina, McNiven, Vanda, Myles-Reid, Diane, Nield, Lynne E., Reuter, Miriam S., Schwartz, Marci L. B., Shannon, Patrick, Silver, Rachel, Somerville, Cherith, Teitelbaum, Ronni, Zahavich, Laura, Bassett, Anne S., Kim, Raymond H., Mital, Seema, Chitayat, David, and Jobling, Rebekah K.

Abstract

Pathogenic variants in NOTCH1are associated with non-syndromic congenital heart disease (CHD) and Adams–Oliver syndrome (AOS). The clinical presentation of individuals with damaging NOTCH1variants is characterized by variable expressivity and incomplete penetrance; however, data on systematic phenotypic characterization are limited. We report the genotype and phenotype of a cohort of 33 individuals (20 females, 13 males; median age 23.4 years, range 2.5–68.3 years) from 11 families with causative NOTCH1variants (9 inherited, 2 de novo; 9 novel), ascertained from a proband with CHD. We describe the cardiac and extracardiac anomalies identified in these 33 individuals, only four of whom met criteria for AOS. The most common CHD identified was tetralogy of Fallot, though various left- and right-sided lesions and septal defects were also present. Extracardiac anomalies identified include cutis aplasia (5/33), cutaneous vascular anomalies (7/33), vascular anomalies of the central nervous system (2/10), Poland anomaly (1/33), pulmonary hypertension (2/33), and structural brain anomalies (3/14). Identification of these findings in a cardiac proband cohort supports NOTCH1-associated CHD and NOTCH1-associated AOS lying on a phenotypic continuum. Our findings also support (1) Broad indications for NOTCH1molecular testing (any familial CHD, simplex tetralogy of Fallot or hypoplastic left heart); (2) Cascade testing in all at-risk relatives; and (3) A thorough physical exam, in addition to cardiac, brain (structural and vascular), abdominal, and ophthalmologic imaging, in all gene-positive individuals. This information is important for guiding the medical management of these individuals, particularly given the high prevalence of NOTCH1variants in the CHD population.

Published
2024
Full Text
View/download PDF

10. The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome

Author

van der Sluijs, Pleuntje J., Jansen, Sandra, Vergano, Samantha A., Adachi-Fukuda, Miho, Alanay, Yasemin, AlKindy, Adila, Baban, Anwar, Bayat, Allan, Beck-Wödl, Stefanie, Berry, Katherine, Bijlsma, Emilia K., Bok, Levinus A., Brouwer, Alwin F. J., van der Burgt, Ineke, Campeau, Philippe M., Canham, Natalie, Chrzanowska, Krystyna, Chu, Yoyo W. Y., Chung, Brain H. Y., Dahan, Karin, De Rademaeker, Marjan, Destree, Anne, Dudding-Byth, Tracy, Earl, Rachel, Elcioglu, Nursel, Elias, Ellen R., Fagerberg, Christina, Gardham, Alice, Gener, Blanca, Gerkes, Erica H., Grasshoff, Ute, van Haeringen, Arie, Heitink, Karin R., Herkert, Johanna C., den Hollander, Nicolette S., Horn, Denise, Hunt, David, Kant, Sarina G., Kato, Mitsuhiro, Kayserili, Hülya, Kersseboom, Rogier, Kilic, Esra, Krajewska-Walasek, Malgorzata, Lammers, Kylin, Laulund, Lone W., Lederer, Damien, Lees, Melissa, López-González, Vanesa, Maas, Saskia, Mancini, Grazia M. S., Marcelis, Carlo, Martinez, Francisco, Maystadt, Isabelle, McGuire, Marianne, McKee, Shane, Mehta, Sarju, Metcalfe, Kay, Milunsky, Jeff, Mizuno, Seiji, Moeschler, John B., Netzer, Christian, Ockeloen, Charlotte W., Oehl-Jaschkowitz, Barbara, Okamoto, Nobuhiko, Olminkhof, Sharon N. M., Orellana, Carmen, Pasquier, Laurent, Pottinger, Caroline, Riehmer, Vera, Robertson, Stephen P., Roifman, Maian, Rooryck, Caroline, Ropers, Fabienne G., Rosello, Monica, Ruivenkamp, Claudia A. L., Sagiroglu, Mahmut S., Sallevelt, Suzanne C. E. H., Sanchis Calvo, Amparo, Simsek-Kiper, Pelin O., Soares, Gabriela, Solaeche, Lucia, Sonmez, Fatma Mujgan, Splitt, Miranda, Steenbeek, Duco, Stegmann, Alexander P. A., Stumpel, Constance T. R. M., Tanabe, Saori, Uctepe, Eyyup, Utine, G. Eda, Veenstra-Knol, Hermine E., Venkateswaran, Sunita, Vilain, Catheline, Vincent-Delorme, Catherine, Vulto-van Silfhout, Anneke T., Wheeler, Patricia, Wilson, Golder N., Wilson, Louise C., Wollnik, Bernd, Kosho, Tomoki, Wieczorek, Dagmar, Eichler, Evan, Pfundt, Rolph, de Vries, Bert B. A., Clayton-Smith, Jill, and Santen, Gijs W. E.

Published
2019
Full Text
View/download PDF

12. A large data resource of genomic copy number variation across neurodevelopmental disorders

Author

Zarrei, Mehdi, Burton, Christie L., Engchuan, Worrawat, Young, Edwin J., Higginbotham, Edward J., MacDonald, Jeffrey R., Trost, Brett, Chan, Ada J. S., Walker, Susan, Lamoureux, Sylvia, Heung, Tracy, Mojarad, Bahareh A., Kellam, Barbara, Paton, Tara, Faheem, Muhammad, Miron, Karin, Lu, Chao, Wang, Ting, Samler, Kozue, Wang, Xiaolin, Costain, Gregory, Hoang, Ny, Pellecchia, Giovanna, Wei, John, Patel, Rohan V., Thiruvahindrapuram, Bhooma, Roifman, Maian, Merico, Daniele, Goodale, Tara, Drmic, Irene, Speevak, Marsha, Howe, Jennifer L., Yuen, Ryan K. C., Buchanan, Janet A., Vorstman, Jacob A. S., Marshall, Christian R., Wintle, Richard F., Rosenberg, David R., Hanna, Gregory L., Woodbury-Smith, Marc, Cytrynbaum, Cheryl, Zwaigenbaum, Lonnie, Elsabbagh, Mayada, Flanagan, Janine, Fernandez, Bridget A., Carter, Melissa T., Szatmari, Peter, Roberts, Wendy, Lerch, Jason, Liu, Xudong, Nicolson, Rob, Georgiades, Stelios, Weksberg, Rosanna, Arnold, Paul D., Bassett, Anne S., Crosbie, Jennifer, Schachar, Russell, Stavropoulos, Dimitri J., Anagnostou, Evdokia, and Scherer, Stephen W.

Published
2019
Full Text
View/download PDF

13. Correction: The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome

Author

van der Sluijs, Pleuntje J., Jansen, Sandra, Vergano, Samantha A., Adachi-Fukuda, Miho, Alanay, Yasemin, AlKindy, Adila, Baban, Anwar, Bayat, Allan, Beck-Wödl, Stefanie, Berry, Katherine, Bijlsma, Emilia K., Bok, Levinus A., Brouwer, Alwin F. J., van der Burgt, Ineke, Campeau, Philippe M., Canham, Natalie, Chrzanowska, Krystyna, Chu, Yoyo W. Y., Chung, Brain H. Y., Dahan, Karin, De Rademaeker, Marjan, Destree, Anne, Dudding-Byth, Tracy, Earl, Rachel, Elcioglu, Nursel, Elias, Ellen R., Fagerberg, Christina, Gardham, Alice, Gener, Blanca, Gerkes, Erica H., Grasshoff, Ute, van Haeringen, Arie, Heitink, Karin R., Herkert, Johanna C., den Hollander, Nicolette S., Horn, Denise, Hunt, David, Kant, Sarina G., Kato, Mitsuhiro, Kayserili, Hülya, Kersseboom, Rogier, Kilic, Esra, Krajewska-Walasek, Malgorzata, Lammers, Kylin, Laulund, Lone W., Lederer, Damien, Lees, Melissa, López-González, Vanesa, Maas, Saskia, Mancini, Grazia M. S., Marcelis, Carlo, Martinez, Francisco, Maystadt, Isabelle, McGuire, Marianne, McKee, Shane, Mehta, Sarju, Metcalfe, Kay, Milunsky, Jeff, Mizuno, Seiji, Moeschler, John B., Netzer, Christian, Ockeloen, Charlotte W., Oehl-Jaschkowitz, Barbara, Okamoto, Nobuhiko, Olminkhof, Sharon N. M., Orellana, Carmen, Pasquier, Laurent, Pottinger, Caroline, Riehmer, Vera, Robertson, Stephen P., Roifman, Maian, Rooryck, Caroline, Ropers, Fabienne G., Rosello, Monica, Ruivenkamp, Claudia A. L., Sagiroglu, Mahmut S., Sallevelt, Suzanne C. E. H., Calvo, Amparo Sanchis, Simsek-Kiper, Pelin O., Soares, Gabriela, Solaeche, Lucia, Sonmez, Fatma Mujgan, Splitt, Miranda, Steenbeek, Duco, Stegmann, Alexander P. A., Stumpel, Constance T. R. M., Tanabe, Saori, Uctepe, Eyyup, Utine, G. Eda, Veenstra-Knol, Hermine E., Venkateswaran, Sunita, Vilain, Catheline, Vincent-Delorme, Catherine, Vulto-van Silfhout, Anneke T., Wheeler, Patricia, Wilson, Golder N., Wilson, Louise C., Wollnik, Bernd, Kosho, Tomoki, Wieczorek, Dagmar, Eichler, Evan, Pfundt, Rolph, de Vries, Bert B. A., Clayton-Smith, Jill, and Santen, Gijs W. E.

Published
2019
Full Text
View/download PDF

14. Anterior extension of the choroid plexus into the frontal horns of the fetal lateral cerebral ventricles: Prenatal findings and postnatal outcome.

Author

Ashwal, Eran, Blaser, Susan, Leckie, Ashley, Kajal, Dilkash, Krishnan, Pradeep, Chong, Karen, Roifman, Maian, Toi, Ants, and Chitayat, David

Abstract

Objective: To evaluate the short‐ and long‐term outcome of fetuses with evidence of extension of the choroid plexus into the frontal horns. Methods: This is a retrospective cohort study of fetuses diagnosed with isolated choroid plexi extending into the frontal horns. Fetuses with major central nervous system anomalies were excluded. Ultrasound and fetal/postnatal magnetic resonance imaging (MRI) were evaluated. Postnatal outcomes, including developmental assessment, were obtained. Results: Twenty nine fetuses were diagnosed with choroid plexus extension (22 unilateral and 7 bilateral). Gestational age at diagnosis was 19.3 weeks. Three cases (10.3%) presented with nonspecific extra‐CNS findings. At presentation, 8/29 (28%) cases had single/multiple choroid plexus cysts (CPC). Twenty‐six (89.6%) cases underwent antenatal MRI. On MRI, four cases had punctate susceptibility weighted imaging (SWI) foci suggesting trace hemosiderin and two cases had ventriculomegaly. Antenatal follow‐up demonstrated resolution of the choroid plexus extension in 90% (18/20). Gestational age at delivery was 39.6 weeks. All had normal neurologic examinations within 24 h of life. Postnatal MRI studies were notable for deep venous differences in seven cases. Long‐term clinical outcome was assessed in 14 cases with a median follow‐up of 1.75 years, with normal neurodevelopment reported in 13/14 (92.8%). Conclusions: Most fetuses with an anterior extension of the choroid plexus as the sole sonographic finding had favorable outcomes. Key points: What is already known about the topic?Differential diagnosis of echogenic matter in the anterior horn varies from a pathologic condition to a normal variant.Literature is scarce concerning the implications of this finding. What does this study add?Most fetuses with an anterior extension of the choroid plexus into the frontal horns have a normal long‐term outcome.Serial imaging is recommended to confirm the lack of any progressive findings.Pre and postnatal MRI may show variations in deep cerebral venous drainage. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

16. Diagnostic yield of genome sequencing for prenatal diagnosis of fetal structural anomalies

Author

Wang, Yiming, primary, Greenfeld, Elena, additional, Watkins, Nicholas, additional, Belesiotis, Peter, additional, Zaidi, Syed H., additional, Marshall, Christian, additional, Thiruvahindrapuram, Bhooma, additional, Shannon, Patrick, additional, Roifman, Maian, additional, Chong, Karen, additional, Chitayat, David, additional, Stavropoulos, Dimitri James, additional, and Noor, Abdul, additional

Published
2022
Full Text
View/download PDF

17. Case Study Contributors

Author

Applegate, Carolyn Dinsmore, Biesecker, Leslie G., Buchanan, Janet A., Carcao, Manuel, Christodoulou, John, Cohn, Iris, Cohn, Ronald Doron, Fahrner, Jill A., Finch, Amy, George-Hyslop, Peter St, Gulati, Ashima, Guthrie, Kelsey, Hamilton, Robert, Hamosh, Ada, Hegele, Robert A., Hitzler, Johann, Hoover-Fong, Julie, Kim, Alexander Y., Kruszka, Paul, Lillicrap, David, Lupski, James R., Mahmud, Farid, Malkin, David, Mallipatna, Ashwin, Martin, Donna, Miller, Kristen, Mu, Weiyi, Narod, Steven, Odame, Isaac, Ours, Christopher A., Pearson, Christopher, Peng, Xiao P., Raraigh, Karen, Rehm, Heidi L., Reuter, Miriam, Roifman, Maian, Roifman, Chaim M., Schatz, Krista, Shoubridge, Eric, Singh, Mandeep, Skuse, David, Thompson, Marisa Gilstrop, Tifft, Cynthia J., Toomey, Christopher B., Vorstman, Jacob A.S., Watnick, Terry J., Weksberg, Rosanna, Wolstencroft, Jeanne, Xiao, Changrui, and Ziegler, Shira G.

Published
2024
Full Text
View/download PDF

18. Mapping the cellular origin and early evolution of leukemia in Down syndrome

Author

Wagenblast, Elvin, primary, Araújo, Joana, additional, Gan, Olga I., additional, Cutting, Sarah K., additional, Murison, Alex, additional, Krivdova, Gabriela, additional, Azkanaz, Maria, additional, McLeod, Jessica L., additional, Smith, Sabrina A., additional, Gratton, Blaise A., additional, Marhon, Sajid A., additional, Gabra, Martino, additional, Medeiros, Jessie J. F., additional, Manteghi, Sanaz, additional, Chen, Jian, additional, Chan-Seng-Yue, Michelle, additional, Garcia-Prat, Laura, additional, Salmena, Leonardo, additional, De Carvalho, Daniel D., additional, Abelson, Sagi, additional, Abdelhaleem, Mohamed, additional, Chong, Karen, additional, Roifman, Maian, additional, Shannon, Patrick, additional, Wang, Jean C. Y., additional, Hitzler, Johann K., additional, Chitayat, David, additional, Dick, John E., additional, and Lechman, Eric R., additional

Published
2021
Full Text
View/download PDF

20. Mapping the Cellular Origin and Early Evolution of Leukemia in Down Syndrome

Author

Wagenblast, Elvin, primary, Araújo, Joana, additional, Gan, Olga I., additional, Cutting, Sarah K., additional, Murison, Alex, additional, Krivdova, Gabriela, additional, Azkanaz, Maria, additional, McLeod, Jessica L., additional, Smith, Sabrina A., additional, Marhon, Sajid A, additional, Gabra, Martino, additional, Chan-Seng-Yue, Michelle, additional, Garcia-Prat, Laura, additional, Salmena, Leonardo, additional, De Carvalho, Daniel D, additional, Chong, Karen, additional, Roifman, Maian, additional, Shannon, Patrick, additional, Wang, Jean C Y, additional, Hitzler, Johann K., additional, Chitayat, David, additional, Dick, John E., additional, and Lechman, Eric R., additional

Published
2020
Full Text
View/download PDF

21. HomozygousGLULdeletion is embryonically viable and leads to glutamine synthetase deficiency

Author

Roifman, Maian, primary, Niles, Kirsten M., additional, MacNeil, Lauren, additional, Blaser, Susan, additional, Noor, Abdul, additional, Godoy, Ruth, additional, Mieghem, Tim, additional, Ryan, Greg, additional, Seaward, Gareth, additional, Sondheimer, Neal, additional, Mercimek‐Andrews, Saadet, additional, Schulze, Andreas, additional, Hewson, Stacy, additional, Ovadia, Adi, additional, Chitayat, David, additional, Morgen, Eric K., additional, Hojilla, Carlo, additional, Kolomietz, Elena, additional, Watkins, Nicholas, additional, Häberle, Johannes, additional, and Shannon, Patrick, additional

Published
2020
Full Text
View/download PDF

22. The variability ofSMARCA4‐related Coffin–Siris syndrome: Do nonsense candidate variants add to milder phenotypes?

Author

Li, Dong, primary, Ahrens‐Nicklas, Rebecca C., additional, Baker, Janice, additional, Bhambhani, Vikas, additional, Calhoun, Amy, additional, Cohen, Julie S., additional, Deardorff, Matthew A., additional, Fernández‐Jaén, Alberto, additional, Kamien, Benjamin, additional, Jain, Mahim, additional, Mckenzie, Fiona, additional, Mintz, Mark, additional, Motter, Constance, additional, Niles, Kirsten, additional, Ritter, Alyssa, additional, Rogers, Curtis, additional, Roifman, Maian, additional, Townshend, Sharron, additional, Ward‐Melver, Catherine, additional, and Schrier Vergano, Samantha A., additional

Published
2020
Full Text
View/download PDF

24. Heterozygous NOTCH1 deletion associated with variable congenital heart defects.

Author

Roifman, Maian, Chung, Brian Hon Yin, Reid, Diane Myles, Teitelbaum, Ronni, Martin, Nicole, Nield, Lynne E., Thompson, Megan, Shannon, Patrick, and Chitayat, David

Subjects
*CONGENITAL heart disease, *MITRAL valve, *AORTIC valve, *DELETION mutation, *HEART valves, *PULMONARY valve, *FETAL heart
Abstract

Pathogenic heterozygous variants in the NOTCH1 gene are known to be associated with both left and right‐sided congenital cardiac anomalies with strikingly incomplete penetrance and variable phenotypic expressivity. De novo NOTCH1 whole gene deletion has been reported rarely in the literature and its association with cardiac defects is less well established. Here, we report four cases of NOTCH1 gene deletion from two families associated with a spectrum of congenital heart defects from bicuspid aortic valve to complex cardiac anomalies. This is the first description of a familial NOTCH1 deletion, showing apparently high penetrance, which may be unique to this mechanism of disease. Immunohistochemical staining of cardiac tissue demonstrated reduced levels of NOTCH1 expression in both the left and right ventricular outflow tracts. These cases suggest that haploinsufficiency caused by NOTCH1 gene deletion is associated with both mild and severe cardiac defects, similar to those caused by pathogenic variants in the gene, but with apparently higher, if not complete, penetrance. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

29. Homozygous GLUL deletion is embryonically viable and leads to glutamine synthetase deficiency.

Author

Roifman, Maian, Niles, Kirsten M., MacNeil, Lauren, Blaser, Susan, Noor, Abdul, Godoy, Ruth, Mieghem, Tim, Ryan, Greg, Seaward, Gareth, Sondheimer, Neal, Mercimek‐Andrews, Saadet, Schulze, Andreas, Hewson, Stacy, Ovadia, Adi, Chitayat, David, Morgen, Eric K., Hojilla, Carlo, Kolomietz, Elena, Watkins, Nicholas, and Häberle, Johannes

Subjects
*GLUTAMINE synthetase, *INBORN errors of metabolism, *DELETION mutation, *DYSTROPHY, *AUTOPSY, *ALLELES, *RECESSIVE genes, *BIOSYNTHESIS
Abstract

Glutamine synthetase (GS) is the enzyme responsible for the biosynthesis of glutamine, providing the only source of endogenous glutamine necessary for several critical metabolic and developmental pathways. GS deficiency, caused by pathogenic variants in the glutamate‐ammonia ligase (GLUL) gene, is a rare autosomal recessive inborn error of metabolism characterized by systemic glutamine deficiency, persistent moderate hyperammonemia, and clinically devastating seizures and multi‐organ failure shortly after birth. The four cases reported thus far were caused by homozygous GLUL missense variants. We report a case of GS deficiency caused by homozygous GLUL gene deletion, diagnosed prenatally and likely representing the most severe end of the spectrum. We expand the known phenotype of this rare condition with novel dysmorphic, radiographic and neuropathologic features identified on post‐mortem examination. The biallelic deletion identified in this case also included the RNASEL gene and was associated with immune dysfunction in the fetus. This case demonstrates that total absence of the GLUL gene in humans is viable beyond the embryonic period, despite the early embryonic lethality found in GLUL animal models. [ABSTRACT FROM AUTHOR]

Published
2020
Full Text
View/download PDF

30. The variability of SMARCA4‐related Coffin–Siris syndrome: Do nonsense candidate variants add to milder phenotypes?

Author

Li, Dong, Ahrens‐Nicklas, Rebecca C., Baker, Janice, Bhambhani, Vikas, Calhoun, Amy, Cohen, Julie S., Deardorff, Matthew A., Fernández‐Jaén, Alberto, Kamien, Benjamin, Jain, Mahim, Mckenzie, Fiona, Mintz, Mark, Motter, Constance, Niles, Kirsten, Ritter, Alyssa, Rogers, Curtis, Roifman, Maian, Townshend, Sharron, Ward‐Melver, Catherine, and Schrier Vergano, Samantha A.

Abstract

SMARCA4 encodes a central ATPase subunit in the BRG1‐/BRM‐associated factors (BAF) or polybromo‐associated BAF (PBAF) complex in humans, which is responsible in part for chromatin remodeling and transcriptional regulation. Variants in this and other genes encoding BAF/PBAF complexes have been implicated in Coffin–Siris Syndrome, a multiple congenital anomaly syndrome classically characterized by learning and developmental differences, coarse facial features, hypertrichosis, and underdevelopment of the fifth digits/nails of the hands and feet. Individuals with SMARCA4 variants have been previously reported and appear to display a variable phenotype. We describe here a cohort of 15 unrelated individuals with SMARCA4 variants from the Coffin–Siris syndrome/BAF pathway disorders registry who further display variability in severity and degrees of learning impairment and health issues. Within this cohort, we also report two individuals with novel nonsense variants who appear to have a phenotype of milder learning/behavioral differences and no organ‐system involvement. [ABSTRACT FROM AUTHOR]

Published
2020
Full Text
View/download PDF

31. TRPV6 Variants Interfere with Maternal-Fetal Calcium Transport through the Placenta and Cause Transient Neonatal Hyperparathyroidism

Author

Suzuki, Yoshiro, primary, Chitayat, David, additional, Sawada, Hirotake, additional, Deardorff, Matthew A., additional, McLaughlin, Heather M., additional, Begtrup, Amber, additional, Millar, Kathryn, additional, Harrington, Jennifer, additional, Chong, Karen, additional, Roifman, Maian, additional, Grand, Katheryn, additional, Tominaga, Makoto, additional, Takada, Fumio, additional, Shuster, Shirley, additional, Obara, Megumi, additional, Mutoh, Hiroshi, additional, Kushima, Reiko, additional, and Nishimura, Gen, additional

Published
2018
Full Text
View/download PDF

32. RAC1 Missense Mutations in Developmental Disorders with Diverse Phenotypes

Author

Reijnders, Margot R.F., primary, Ansor, Nurhuda M., additional, Kousi, Maria, additional, Yue, Wyatt W., additional, Tan, Perciliz L., additional, Clarkson, Katie, additional, Clayton-Smith, Jill, additional, Corning, Ken, additional, Jones, Julie R., additional, Lam, Wayne W.K., additional, Mancini, Grazia M.S., additional, Marcelis, Carlo, additional, Mohammed, Shehla, additional, Pfundt, Rolph, additional, Roifman, Maian, additional, Cohn, Ronald, additional, Chitayat, David, additional, Millard, Tom H., additional, Katsanis, Nicholas, additional, Brunner, Han G., additional, and Banka, Siddharth, additional

Published
2017
Full Text
View/download PDF

34. Whole-genome sequencing expands diagnostic utility and improves clinical management in paediatric medicine

Author

Stavropoulos, Dimitri J, primary, Merico, Daniele, additional, Jobling, Rebekah, additional, Bowdin, Sarah, additional, Monfared, Nasim, additional, Thiruvahindrapuram, Bhooma, additional, Nalpathamkalam, Thomas, additional, Pellecchia, Giovanna, additional, Yuen, Ryan K C, additional, Szego, Michael J, additional, Hayeems, Robin Z, additional, Shaul, Randi Zlotnik, additional, Brudno, Michael, additional, Girdea, Marta, additional, Frey, Brendan, additional, Alipanahi, Babak, additional, Ahmed, Sohnee, additional, Babul-Hirji, Riyana, additional, Porras, Ramses Badilla, additional, Carter, Melissa T, additional, Chad, Lauren, additional, Chaudhry, Ayeshah, additional, Chitayat, David, additional, Doust, Soghra Jougheh, additional, Cytrynbaum, Cheryl, additional, Dupuis, Lucie, additional, Ejaz, Resham, additional, Fishman, Leona, additional, Guerin, Andrea, additional, Hashemi, Bita, additional, Helal, Mayada, additional, Hewson, Stacy, additional, Inbar-Feigenberg, Michal, additional, Kannu, Peter, additional, Karp, Natalya, additional, Kim, Raymond H, additional, Kronick, Jonathan, additional, Liston, Eriskay, additional, MacDonald, Heather, additional, Mercimek-Mahmutoglu, Saadet, additional, Mendoza-Londono, Roberto, additional, Nasr, Enas, additional, Nimmo, Graeme, additional, Parkinson, Nicole, additional, Quercia, Nada, additional, Raiman, Julian, additional, Roifman, Maian, additional, Schulze, Andreas, additional, Shugar, Andrea, additional, Shuman, Cheryl, additional, Sinajon, Pierre, additional, Siriwardena, Komudi, additional, Weksberg, Rosanna, additional, Yoon, Grace, additional, Carew, Chris, additional, Erickson, Raith, additional, Leach, Richard A, additional, Klein, Robert, additional, Ray, Peter N, additional, Meyn, M Stephen, additional, Scherer, Stephen W, additional, Cohn, Ronald D, additional, and Marshall, Christian R, additional

Published
2016
Full Text
View/download PDF

35. Compound heterozygous mutations in the noncoding RNU4ATAC cause Roifman Syndrome by disrupting minor intron splicing

Author

Merico, Daniele, primary, Roifman, Maian, additional, Braunschweig, Ulrich, additional, Yuen, Ryan K. C., additional, Alexandrova, Roumiana, additional, Bates, Andrea, additional, Reid, Brenda, additional, Nalpathamkalam, Thomas, additional, Wang, Zhuozhi, additional, Thiruvahindrapuram, Bhooma, additional, Gray, Paul, additional, Kakakios, Alyson, additional, Peake, Jane, additional, Hogarth, Stephanie, additional, Manson, David, additional, Buncic, Raymond, additional, Pereira, Sergio L., additional, Herbrick, Jo-Anne, additional, Blencowe, Benjamin J., additional, Roifman, Chaim M., additional, and Scherer, Stephen W., additional

Published
2015
Full Text
View/download PDF

37. The ARID1B spectrum in 143 patients

Author

Catherine Vincent-Delorme, Claudia A. L. Ruivenkamp, Marjan De Rademaeker, Francisco Martínez, Tracy Dudding-Byth, Marianne McGuire, Bert B.A. de Vries, Mitsuhiro Kato, Levinus A. Bok, Hülya Kayserili, Jeff M. Milunsky, Suzanne C E H Sallevelt, Alwin F. J. Brouwer, Jill Clayton-Smith, Emilia K. Bijlsma, Miranda Splitt, Patricia G. Wheeler, Philippe M. Campeau, Fatma Mujgan Sonmez, Kylin Lammers, Stefanie Beck-Wödl, Caroline Rooryck, Louise C. Wilson, Evan E. Eichler, Sarina G. Kant, Johanna C. Herkert, Karin R. Heitink, Eyyup Uctepe, Pleuntje J. van der Sluijs, Miho Adachi-Fukuda, Lone W. Laulund, Sandra Jansen, Nicolette S. den Hollander, Damien Lederer, Tomoki Kosho, Constance T. R. M. Stumpel, Saskia M. Maas, Esra Kılıç, Erica H. Gerkes, Duco Steenbeek, Melissa Lees, Kay Metcalfe, Karin Dahan, Ineke van der Burgt, Isabelle Maystadt, Christian Netzer, Ute Grasshoff, Carmen Orellana, Mahmut Şamil Sağıroğlu, Gijs W. E. Santen, Pelin Ozlem Simsek-Kiper, Mónica Roselló, Gabriela Soares, Alexander P.A. Stegmann, Stephen P. Robertson, Adila Al-Kindy, Maian Roifman, Saori Tanabe, Vera Riehmer, Brain H Y Chung, Arie van Haeringen, G. Eda Utine, Yasemin Alanay, Rogier Kersseboom, John B. Moeschler, Barbara Oehl-Jaschkowitz, Katherine Berry, Denise Horn, Alice Gardham, Shane McKee, Anwar Baban, Amparo Sanchis Calvo, Golder N. Wilson, Krystyna H. Chrzanowska, G. M. S. Mancini, Ellen R. Elias, Małgorzata Krajewska-Walasek, Rolph Pfundt, Sarju G. Mehta, Fabienne G. Ropers, Seiji Mizuno, David Hunt, Caroline Pottinger, Dagmar Wieczorek, Yoyo W. Y. Chu, Laurent Pasquier, Bernd Wollnik, Nobuhiko Okamoto, Sunita Venkateswaran, Vanesa López-González, Natalie Canham, Blanca Gener, Anne Destree, Christina Fagerberg, Rachel K. Earl, Sharon N M Olminkhof, Nursel Elcioglu, Charlotte W. Ockeloen, Carlo Marcelis, Samantha A. Vergano, Hermine E. Veenstra-Knol, Anneke T. Vulto-van Silfhout, Allan Bayat, Catheline Vilain, Lucia Solaeche, MUMC+: DA KG Polikliniek (9), RS: GROW - R4 - Reproductive and Perinatal Medicine, Genetica & Celbiologie, MUMC+: DA KG Lab Centraal Lab (9), MUMC+: DA Pat Cytologie (9), Klinische Genetica, van der Sluijs, Pleuntje J., Jansen, Sandra, Vergano, Samantha A., Adachi-Fukuda, Miho, Alanay, Yasemin, AlKindy, Adila, Baban, Anwar, Bayat, Allan, Beck-Woedl, Stefanie, Berry, Katherine, Bijlsma, Emilia K., Bok, Levinus A., Brouwer, Alwin F. J., van der Burgt, Ineke, Campeau, Philippe M., Canham, Natalie, Chrzanowska, Krystyna, Chu, Yoyo W. Y., Chung, Brain H. Y., Dahan, Karin, De Rademaeker, Marjan, Destree, Anne, Dudding-Byth, Tracy, Earl, Rachel, Elcioglu, Nursel, Elias, Ellen R., Fagerberg, Christina, Gardham, Alice, Gener, Blanca, Gerkes, Erica H., Grasshoff, Ute, van Haeringen, Arie, Heitink, Karin R., Herkert, Johanna C., den Hollander, Nicolette S., Horn, Denise, Hunt, David, Kant, Sarina G., Kato, Mitsuhiro, Kayserili, Hulya, Kersseboom, Rogier, Kilic, Esra, Krajewska-Walasek, Malgorzata, Lammers, Kylin, Laulund, Lone W., Lederer, Damien, Lees, Melissa, Lopez-Gonzalez, Vanesa, Maas, Saskia, Mancini, Grazia M. S., Marcelis, Carlo, Martinez, Francisco, Maystadt, Isabelle, McGuire, Marianne, McKee, Shane, Mehta, Sarju, Metcalfe, Kay, Milunsky, Jeff, Mizuno, Seiji, Moeschler, John B., Netzer, Christian, Ockeloen, Charlotte W., Oehl-Jaschkowitz, Barbara, Okamoto, Nobuhiko, Olminkhof, Sharon N. M., Orellana, Carmen, Pasquier, Laurent, Pottinger, Caroline, Riehmer, Vera, Robertson, Stephen P., Roifman, Maian, Rooryck, Caroline, Ropers, Fabienne G., Rosello, Monica, Ruivenkamp, Claudia A. L., Sagiroglu, Mahmut S., Sallevelt, Suzanne C. E. H., Sanchis Calvo, Amparo, Simsek-Kiper, Pelin O., Soares, Gabriela, Solaeche, Lucia, Sonmez, Fatma Mujgan, Splitt, Miranda, Steenbeek, Duco, Stegmann, Alexander P. A., Stumpel, Constance T. R. M., Tanabe, Saori, Uctepe, Eyyup, Utine, G. Eda, Veenstra-Knol, Hermine E., Venkateswaran, Sunita, Vilain, Catheline, Vincent-Delorme, Catherine, Vulto-van Silfhout, Anneke T., Wheeler, Patricia, Wilson, Golder N., Wilson, Louise C., Wollnik, Bernd, Kosho, Tomoki, Wieczorek, Dagmar, Eichler, Evan, Pfundt, Rolph, de Vries, Bert B. A., Clayton-Smith, Jill, Santen, Gijs W. E., Erasmus MC other, Clinical Genetics, Human Genetics, and Acibadem University Dspace

Subjects
Male, 0301 basic medicine, Hypertrichosis, Pediatrics, cuello, bias, Coffin–Siris syndrome, Chromosomal Proteins, Non-Histone, humanos, adolescente, Penetrance, PHENOTYPE, 0302 clinical medicine, Genotype, Intellectual disability, Exome, Coffin-Siris syndrome, Child, mediana edad, Genetics (clinical), Exome sequencing, factores de transcripción, adulto, Middle Aged, estudios de asociación genética, 3. Good health, DNA-Binding Proteins, intellectual disability, Child, Preschool, discapacidad intelectual, penetrancia, Female, Hand Deformities, Congenital, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], Adult, medicine.medical_specialty, Adolescent, Micrognathism, Article, CHROMATIN-REMODELING COMPLEX, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, cara, micrognatismo, Human Phenotype Ontology, medicine, Humans, Abnormalities, Multiple, mutación, Long eyelashes, Genetic Association Studies, lactante, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], business.industry, MUTATIONS, proteínas de unión al ADN, Infant, Newborn, Genetic Variation, Infant, ARID1B, Hand Deformities, Phalanx, medicine.disease, variación genética, deformidades de la mano, exoma, 030104 developmental biology, Face, Mutation, business, Neck, 030217 neurology & neurosurgery, Transcription Factors
Abstract

Purpose: Pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin-Siris patients (ARID1BCSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. Methods: Clinicians entered clinical data in an extensive webbased survey. Results: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. Conclusion: There are only minor differences between ARID1BID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features., We are grateful for the assistance of Pepijn Cox in setting up the website www.arid1bgene.com. This study has made use of data generated by the Human Disease Genes website series, www.humandiseasegenes.com. This work was financially supported by grants from the Netherlands Organisation for Health Research and Development (917-86-319 to B.B.A.d.V., 912-12-109 to B.B.A.d.V.)

Published
2019

38. Homozygous GLUL deletion is embryonically viable and leads to glutamine synthetase deficiency

Author

Saadet Mercimek-Andrews, Stacy Hewson, David Chitayat, Elena Kolomietz, Neal Sondheimer, Nicholas A. Watkins, Abdul Noor, Eric K. Morgen, Andreas Schulze, Ruth Godoy, Carlo Hojilla, Susan Blaser, Tim Van Mieghem, Maian Roifman, Kirsten M. Niles, Johannes Häberle, Adi Ovadia, Lauren G. MacNeil, Greg Ryan, Patrick Shannon, Gareth Seaward, University of Zurich, and Roifman, Maian

Subjects
0301 basic medicine, Adult, Male, 2716 Genetics (clinical), Glutamine, 610 Medicine & health, 030105 genetics & heredity, Biology, 03 medical and health sciences, Fetus, Metabolic Diseases, 1311 Genetics, Glutamate-Ammonia Ligase, Glutamine synthetase, Genetics, medicine, Missense mutation, Humans, Gene, Amino Acid Metabolism, Inborn Errors, Genetics (clinical), Homozygote, Infant, Newborn, RNASEL Gene, Hyperammonemia, medicine.disease, Phenotype, 030104 developmental biology, Inborn error of metabolism, 10036 Medical Clinic, Female
Abstract

Glutamine synthetase (GS) is the enzyme responsible for the biosynthesis of glutamine, providing the only source of endogenous glutamine necessary for several critical metabolic and developmental pathways. GS deficiency, caused by pathogenic variants in the glutamate-ammonia ligase (GLUL) gene, is a rare autosomal recessive inborn error of metabolism characterized by systemic glutamine deficiency, persistent moderate hyperammonemia, and clinically devastating seizures and multi-organ failure shortly after birth. The four cases reported thus far were caused by homozygous GLUL missense variants. We report a case of GS deficiency caused by homozygous GLUL gene deletion, diagnosed prenatally and likely representing the most severe end of the spectrum. We expand the known phenotype of this rare condition with novel dysmorphic, radiographic and neuropathologic features identified on post-mortem examination. The biallelic deletion identified in this case also included the RNASEL gene and was associated with immune dysfunction in the fetus. This case demonstrates that total absence of the GLUL gene in humans is viable beyond the embryonic period, despite the early embryonic lethality found in GLUL animal models.

Published
2020

39. The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome

Author

Karabey, Hülya Kayserili (ORCID 0000-0003-0376-499X & YÖK ID 7945), van der Sluijs, Pleuntje J., Jansen, Sandra, Vergano, Samantha A., Adachi-Fukuda, Miho, Alanay, Yasemin, AlKindy, Adila, Baban, Anwar, Bayat, Allan, Beck-Woedl, Stefanie, Berry, Katherine, Bijlsma, Emilia K., Bok, Levinus A., Brouwer, Alwin F. J., van der Burgt, Ineke, Campeau, Philippe M., Canham, Natalie, Chrzanowska, Krystyna, Chu, Yoyo W. Y., Chung, Brain H. Y., Dahan, Karin, De Rademaeker, Marjan, Destree, Anne, Dudding-Byth, Tracy, Earl, Rachel, Elçioğlu, Nursel, Elias, Ellen R., Fagerberg, Christina, Gardham, Alice, Gener, Blanca, Gerkes, Erica H., Grasshoff, Ute, van Haeringen, Arie, Heitink, Karin R., Herkert, Johanna C., den Hollander, Nicolette S., Horn, Denise, Hunt, David, Kant, Sarina G., Kato, Mitsuhiro, Kersseboom, Rogier, Kılıç, Esra, Krajewska-Walasek, Malgorzata, Lammers, Kylin, Laulund, Lone W., Lederer, Damien, Lees, Melissa, Lopez-Gonzalez, Vanesa, Maas, Saskia, Mancini, Grazia M. S., Marcelis, Carlo, Martinez, Francisco, Maystadt, Isabelle, McGuire, Marianne, McKee, Shane, Mehta, Sarju, Metcalfe, Kay, Milunsky, Jeff, Mizuno, Seiji, Moeschler, John B., Netzer, Christian, Ockeloen, Charlotte W., Oehl-Jaschkowitz, Barbara, Okamoto, Nobuhiko, Olminkhof, Sharon N. M., Orellana, Carmen, Pasquier, Laurent, Pottinger, Caroline, Riehmer, Vera, Robertson, Stephen P., Roifman, Maian, Rooryck, Caroline, Ropers, Fabienne G., Rosello, Monica, Ruivenkamp, Claudia A. L., Sağıroğlu, Mahmut S., Sallevelt, Suzanne C. E. H., Sanchis Calvo, Amparo, Şimşek-Kiper, Pelin O., Soares, Gabriela, Solaeche, Lucia, Sönmez, Fatma Müjgan, Splitt, Miranda, Steenbeek, Duco, Stegmann, Alexander P. A., Stumpel, Constance T. R. M., Tanabe, Saori, Üçtepe, Eyyüp, Utine, G. Eda, Veenstra-Knol, Hermine E., Venkateswaran, Sunita, Vilain, Catheline, Vincent-Delorme, Catherine, Vulto-van Silfhout, Anneke T., Wheeler, Patricia, Wilson, Golder N., Wilson, Louise C., Wollnik, Bernd, Kosho, Tomoki, Wieczorek, Dagmar, Eichler, Evan, Pfundt, Rolph, de Vries, Bert B. A., Clayton-Smith, Jill, Santen, Gijs W. E., School of Medicine, and Department of Medical Genetics

Subjects
Medicine, Genetics and heredity, ARID1B, Bias, Coffin–Siris syndrome, Intellectual disability
Abstract

Purpose: pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin–Siris patients (ARID1B-CSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. Methods: clinicians entered clinical data in an extensive web-based survey. Results: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. Conclusion: there are only minor differences between ARID1B-ID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features., Netherlands Organisation for Health Research and Development

Published
2019

40. Autosomal Dominant Robinow Syndrome

Author

Roifman M, Brunner H, Lohr J, Mazzeu J, Chitayat D, Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G, and Amemiya A

Abstract

Clinical Characteristics: Autosomal dominant Robinow syndrome (ADRS) is characterized by skeletal findings (short stature, mesomelic limb shortening predominantly of the upper limbs, and brachydactyly), genital abnormalities (in males: micropenis / webbed penis, hypoplastic scrotum, cryptorchidism; in females: hypoplastic clitoris and labia majora), dysmorphic facial features (widely spaced and prominent eyes, frontal bossing, anteverted nares, midface retrusion), dental abnormalities (including malocclusion, crowding, hypodontia, late eruption of permanent teeth), bilobed tongue, and occasional prenatal macrocephaly that persists postnatally. Less common findings include renal anomalies, radial head dislocation, vertebral abnormalities such as hemivertebrae and scoliosis, nail dysplasia, cardiac defects, cleft lip/palate, and (rarely) cognitive delay. When present, cardiac defects are a major cause of morbidity and mortality. A variant of Robinow syndrome, associated with osteosclerosis and caused by a heterozygous pathogenic variant in DVL1 , is characterized by normal stature, persistent macrocephaly, increased bone mineral density with skull osteosclerosis, and hearing loss, in addition to the typical features described above., Diagnosis/testing: The diagnosis of autosomal dominant Robinow syndrome is established in a proband with typical suggestive findings and/or by the identification of a heterozygous pathogenic variant in DVL1 , DVL3 , or WNT5A through molecular genetic testing., Management: Treatment of manifestations: Corrective surgeries as needed for cryptorchidism, abnormal penile insertion / penoscrotal position, and cleft lip/palate. Hormone therapy may be helpful for males with micropenis. Orthodontic treatment is typically required. Surveillance: Measurement of head circumference regularly in infancy and throughout childhood. Developmental assessment every three months in infancy and every six months to one year thereafter, or more frequently as needed if cognitive delays are identified. Dental evaluation every six to 12 months or as recommended. Periodic hearing assessments in childhood. Regular cardiac and renal assessment as needed by respective specialists if abnormalities are identified. Evaluation of relatives at risk: Evaluation of the sibs of a proband in order to identify as early as possible those who would benefit from institution of treatment and surveillance. Pregnancy management: Pregnancy in affected women appears to be generally uncomplicated. For an affected fetus, cesarean section may be required for abnormal presentation and/or cephalopelvic disproportion., Genetic Counseling: ADRS is inherited in an autosomal dominant manner. A proband may have the disorder as a result of either an inherited or de novo pathogenic variant. Each child of an individual with ADRS has a 50% chance of inheriting the pathogenic variant; however, the severity of the clinical manifestations cannot be predicted from the results of molecular genetic testing. Prenatal testing for pregnancies at increased risk is possible if the DVL1 , DVL3 , or WNT5A pathogenic variant has been identified in an affected family member., (Copyright © 1993-2021, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.)

Published
1993

Catalog

Books, media, physical & digital resources
See catalog results