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13 results on '"Aten, Emmelien"'

1. Consensus recommendations on organization of care for individuals with Phelan-McDermid syndrome

Author

van Eeghen, A. M., Gaasterland, C. M.W., Haneveld, M. J.Klein, Stemkens, D., Fernández-Fructuoso, José Ramón, Maruani, Anna, Hadzsiev, K., Hadzsiev, Kinga, van Balkom, Ingrid D.C., Alhambra, Norma, Anderlid, Britt Marie, Andres, Stephanie, Aten, Emmelien, Guedes, Rui Barbosa, Bonaglia, Maria C., Bourgeron, Thomas, Burdeus-Olavarrieta, Monica, Carbin, Maya J., Kuiper, Els, Cooke, Jennifer, Damstra, Robert J., de Coo, Irenaeus F.M., Di Domenico, Stella, Evans, D. Gareth, Grabrucker, Andreas M., Gunnarson, Cecilia, Hennekam, Raoul C., Jesse, Sarah, Kant, Sarina G., Koza, Sylvia A., van Ravenswaaij-Arts, Conny M.A., Walinga, Margreet, Landlust, Annemiek M., van Eeghen, A. M., Gaasterland, C. M.W., Haneveld, M. J.Klein, Stemkens, D., Fernández-Fructuoso, José Ramón, Maruani, Anna, Hadzsiev, K., Hadzsiev, Kinga, van Balkom, Ingrid D.C., Alhambra, Norma, Anderlid, Britt Marie, Andres, Stephanie, Aten, Emmelien, Guedes, Rui Barbosa, Bonaglia, Maria C., Bourgeron, Thomas, Burdeus-Olavarrieta, Monica, Carbin, Maya J., Kuiper, Els, Cooke, Jennifer, Damstra, Robert J., de Coo, Irenaeus F.M., Di Domenico, Stella, Evans, D. Gareth, Grabrucker, Andreas M., Gunnarson, Cecilia, Hennekam, Raoul C., Jesse, Sarah, Kant, Sarina G., Koza, Sylvia A., van Ravenswaaij-Arts, Conny M.A., Walinga, Margreet, and Landlust, Annemiek M.

Abstract

The manifestations of Phelan-McDermid syndrome (PMS) are complex, warranting expert and multidisciplinary care in all life stages. In the present paper we propose consensus recommendations on the organization of care for individuals with PMS. We indicate that care should consider all life domains, which can be done within the framework of the International Classification of Functioning, Disability and Health (ICF). This framework assesses disability and functioning as the outcome of the individual's interactions with other factors. The different roles within care, such as performed by a centre of expertise, by regional health care providers and by a coordinating physician are addressed. A surveillance scheme and emergency card is provided and disciplines participating in a multidisciplinary team for PMS are described. Additionally, recommendations are provided for transition from paediatric to adult care. This care proposition may also be useful for individuals with other rare genetic neurodevelopmental disorders.

Published
2023

2. Consensus recommendations on counselling in Phelan-McDermid syndrome, with special attention to recurrence risk and to ring chromosome 22

Author

Koza, Sylvia A., Tabet, Anne C., Bonaglia, Maria C., Andres, Stephanie, Anderlid, Britt Marie, Aten, Emmelien, Stiefsohn, Dominique, Evans, D. Gareth, van Ravenswaaij-Arts, Conny M.A., Kant, Sarina G., Koza, Sylvia A., Tabet, Anne C., Bonaglia, Maria C., Andres, Stephanie, Anderlid, Britt Marie, Aten, Emmelien, Stiefsohn, Dominique, Evans, D. Gareth, van Ravenswaaij-Arts, Conny M.A., and Kant, Sarina G.

Abstract

This paper focuses on genetic counselling in Phelan-McDermid syndrome (PMS), a rare neurodevelopmental disorder caused by a deletion 22q13.3 or a pathogenic variant in SHANK3. It is one of a series of papers written by the European PMS consortium as a consensus guideline. We reviewed the available literature based on pre-set questions to formulate recommendations on counselling, diagnostic work-up and surveillance for tumours related to ring chromosome 22. All recommendations were approved by the consortium, which consists of professionals and patient representatives, using a voting procedure. PMS can only rarely be diagnosed based solely on clinical features and requires confirmation via genetic testing. In most cases, the family will be referred to a clinical geneticist for counselling after the genetic diagnosis has been made. Family members will be investigated and, if indicated, the chance of recurrence discussed with them. Most individuals with PMS have a de novo deletion or a pathogenic variant of SHANK3. The 22q13.3 deletion can be a simple deletion, a ring chromosome 22, or the result of a parental balanced chromosomal anomaly, influencing the risk of recurrence. Individuals with a ring chromosome 22 have an increased risk of NF2-related schwannomatosis (formerly neurofibromatosis type 2) and atypical teratoid rhabdoid tumours, which are associated with the tumour-suppressor genes NF2 and SMARCB1, respectively, and both genes are located on chromosome 22. The prevalence of PMS due to a ring chromosome 22 is estimated to be 10–20%. The risk of developing a tumour in an individual with a ring chromosome 22 can be calculated as 2–4%. However, those individuals who do develop tumours often have multiple. We recommend referring all individuals with PMS and their parents to a clinical geneticist or a comparably experienced medical specialist for genetic counselling, further genetic testing, follow-up and discussion of prenatal diagnostic testing in subsequent

Published
2023

3. High-yield identification of pathogenic NF1 variants by skin fibroblast transcriptome screening after apparently normal diagnostic DNA testing

Author

Douben, Hannie C.W., Nellist, Mark, van Unen, Leontine, Elfferich, Peter, Kasteleijn, Esmee, Hoogeveen-Westerveld, Marianne, Louwen, Jesse, van Veghel-Plandsoen, Monique, de Valk, Walter, Saris, Jasper J., Hendriks, Femke, Korpershoek, Esther, Hoefsloot, Lies H., van Vliet, Margreethe, van Bever, Yolande, van de Laar, Ingrid, Aten, Emmelien, Lachmeijer, Augusta M.A., Taal, Walter, van den Bersselaar, Lisa, Schuurmans, Juliette, Oostenbrink, Rianne, van Minkelen, Rick, van Ierland, Yvette, van Ham, Tjakko J., Douben, Hannie C.W., Nellist, Mark, van Unen, Leontine, Elfferich, Peter, Kasteleijn, Esmee, Hoogeveen-Westerveld, Marianne, Louwen, Jesse, van Veghel-Plandsoen, Monique, de Valk, Walter, Saris, Jasper J., Hendriks, Femke, Korpershoek, Esther, Hoefsloot, Lies H., van Vliet, Margreethe, van Bever, Yolande, van de Laar, Ingrid, Aten, Emmelien, Lachmeijer, Augusta M.A., Taal, Walter, van den Bersselaar, Lisa, Schuurmans, Juliette, Oostenbrink, Rianne, van Minkelen, Rick, van Ierland, Yvette, and van Ham, Tjakko J.

Abstract

Neurofibromatosis type 1 (NF1) is caused by inactivating mutations in NF1. Due to the size, complexity, and high mutation rate at the NF1 locus, the identification of causative variants can be challenging. To obtain a molecular diagnosis in 15 individuals meeting diagnostic criteria for NF1, we performed transcriptome analysis (RNA-seq) on RNA obtained from cultured skin fibroblasts. In each case, routine molecular DNA diagnostics had failed to identify a disease-causing variant in NF1. A pathogenic variant or abnormal mRNA splicing was identified in 13 cases: 6 deep intronic variants and 2 transposon insertions causing noncanonical splicing, 3 postzygotic changes, 1 branch point mutation and, in 1 case, abnormal splicing for which the responsible DNA change remains to be identified. These findings helped resolve the molecular findings for an additional 17 individuals in multiple families with NF1, demonstrating the utility of skin-fibroblast-based transcriptome analysis for molecular diagnostics. RNA-seq improves mutation detection in NF1 and provides a powerful complementary approach to DNA-based methods. Importantly, our approach is applicable to other genetic disorders, particularly those caused by a wide variety of variants in a limited number of genes and specifically for individuals in whom routine molecular DNA diagnostics did not identify the causative variant.

Published
2022

4. Correction : Putting genome-wide sequencing in neonates into perspective

Author

van der Sluijs, Pleuntje J., Aten, Emmelien, Barge-Schaapveld, Daniela Q.C.M., Bijlsma, Emilia K., Bökenkamp-Gramann, Regina, Kaat, Laura Donker, van Doorn, Remco, van de Putte, Dietje Fransen, van Haeringen, Arie, ten Harkel, Arend D.J., Hilhorst-Hofstee, Yvonne, Hoffer, Mariette J.V., den Hollander, Nicolette S., van Ierland, Yvette, Koopmans, Marije, Kriek, Marjolein, Moghadasi, Setareh, Nibbeling, Esther A.R., Peeters-Scholte, Cacha M.P.C.D., Potjer, Thomas P., van Rij, Maartje, Ruivenkamp, Claudia A.L., Rutten, Julie W., Steggerda, Sylke J., Suerink, Manon, Tan, Ratna N.G.B., van der Tuin, Karin, Visser, Remco, van der Werf–t Lam, Anne Sophie, Williams, Monique, Witlox, Ruben, Santen, Gijs W.E., van der Sluijs, Pleuntje J., Aten, Emmelien, Barge-Schaapveld, Daniela Q.C.M., Bijlsma, Emilia K., Bökenkamp-Gramann, Regina, Kaat, Laura Donker, van Doorn, Remco, van de Putte, Dietje Fransen, van Haeringen, Arie, ten Harkel, Arend D.J., Hilhorst-Hofstee, Yvonne, Hoffer, Mariette J.V., den Hollander, Nicolette S., van Ierland, Yvette, Koopmans, Marije, Kriek, Marjolein, Moghadasi, Setareh, Nibbeling, Esther A.R., Peeters-Scholte, Cacha M.P.C.D., Potjer, Thomas P., van Rij, Maartje, Ruivenkamp, Claudia A.L., Rutten, Julie W., Steggerda, Sylke J., Suerink, Manon, Tan, Ratna N.G.B., van der Tuin, Karin, Visser, Remco, van der Werf–t Lam, Anne Sophie, Williams, Monique, Witlox, Ruben, and Santen, Gijs W.E.

Published
2019

5. Correction : Putting genome-wide sequencing in neonates into perspective

Author

van der Sluijs, Pleuntje J., Aten, Emmelien, Barge-Schaapveld, Daniela Q.C.M., Bijlsma, Emilia K., Bökenkamp-Gramann, Regina, Kaat, Laura Donker, van Doorn, Remco, van de Putte, Dietje Fransen, van Haeringen, Arie, ten Harkel, Arend D.J., Hilhorst-Hofstee, Yvonne, Hoffer, Mariette J.V., den Hollander, Nicolette S., van Ierland, Yvette, Koopmans, Marije, Kriek, Marjolein, Moghadasi, Setareh, Nibbeling, Esther A.R., Peeters-Scholte, Cacha M.P.C.D., Potjer, Thomas P., van Rij, Maartje, Ruivenkamp, Claudia A.L., Rutten, Julie W., Steggerda, Sylke J., Suerink, Manon, Tan, Ratna N.G.B., van der Tuin, Karin, Visser, Remco, van der Werf–t Lam, Anne Sophie, Williams, Monique, Witlox, Ruben, Santen, Gijs W.E., van der Sluijs, Pleuntje J., Aten, Emmelien, Barge-Schaapveld, Daniela Q.C.M., Bijlsma, Emilia K., Bökenkamp-Gramann, Regina, Kaat, Laura Donker, van Doorn, Remco, van de Putte, Dietje Fransen, van Haeringen, Arie, ten Harkel, Arend D.J., Hilhorst-Hofstee, Yvonne, Hoffer, Mariette J.V., den Hollander, Nicolette S., van Ierland, Yvette, Koopmans, Marije, Kriek, Marjolein, Moghadasi, Setareh, Nibbeling, Esther A.R., Peeters-Scholte, Cacha M.P.C.D., Potjer, Thomas P., van Rij, Maartje, Ruivenkamp, Claudia A.L., Rutten, Julie W., Steggerda, Sylke J., Suerink, Manon, Tan, Ratna N.G.B., van der Tuin, Karin, Visser, Remco, van der Werf–t Lam, Anne Sophie, Williams, Monique, Witlox, Ruben, and Santen, Gijs W.E.

Published
2019

6. Correction: Putting genome-wide sequencing in neonates into perspective

Author

Genetica Klinische Genetica, Cancer, van der Sluijs, Pleuntje J., Aten, Emmelien, Barge-Schaapveld, Daniela Q.C.M., Bijlsma, Emilia K., Bökenkamp-Gramann, Regina, Kaat, Laura Donker, van Doorn, Remco, van de Putte, Dietje Fransen, van Haeringen, Arie, ten Harkel, Arend D.J., Hilhorst-Hofstee, Yvonne, Hoffer, Mariette J.V., den Hollander, Nicolette S., van Ierland, Yvette, Koopmans, Marije, Kriek, Marjolein, Moghadasi, Setareh, Nibbeling, Esther A.R., Peeters-Scholte, Cacha M.P.C.D., Potjer, Thomas P., van Rij, Maartje, Ruivenkamp, Claudia A.L., Rutten, Julie W., Steggerda, Sylke J., Suerink, Manon, Tan, Ratna N.G.B., van der Tuin, Karin, Visser, Remco, van der Werf–t Lam, Anne Sophie, Williams, Monique, Witlox, Ruben, Santen, Gijs W.E., Genetica Klinische Genetica, Cancer, van der Sluijs, Pleuntje J., Aten, Emmelien, Barge-Schaapveld, Daniela Q.C.M., Bijlsma, Emilia K., Bökenkamp-Gramann, Regina, Kaat, Laura Donker, van Doorn, Remco, van de Putte, Dietje Fransen, van Haeringen, Arie, ten Harkel, Arend D.J., Hilhorst-Hofstee, Yvonne, Hoffer, Mariette J.V., den Hollander, Nicolette S., van Ierland, Yvette, Koopmans, Marije, Kriek, Marjolein, Moghadasi, Setareh, Nibbeling, Esther A.R., Peeters-Scholte, Cacha M.P.C.D., Potjer, Thomas P., van Rij, Maartje, Ruivenkamp, Claudia A.L., Rutten, Julie W., Steggerda, Sylke J., Suerink, Manon, Tan, Ratna N.G.B., van der Tuin, Karin, Visser, Remco, van der Werf–t Lam, Anne Sophie, Williams, Monique, Witlox, Ruben, and Santen, Gijs W.E.

Published
2019

7. Lamin A/C-Related Cardiac Disease : Late Onset With a Variable and Mild Phenotype in a Large Cohort of Patients With the Lamin A/C p.(Arg331Gln) Founder Mutation

Author

Hoorntje, Edgar T, Bollen, Ilse Ae, Barge-Schaapveld, Daniela Q, Van Tienen, Florence H J, Te Meerman, Gerard J, Jansweijer, Joeri A, van Essen, Anthonie J, Volders, Paul G. A., Constantinescu, Alina, Van Den Akker, Peter C., van Spaendonck-Zwarts, Karin Y., Oldenburg, Rogier A, Marcelis, Carlo L. M., van der Smagt, Jasper J, Hennekam, Eric A, Vink, Aryan, Bootsma, Marianne, Aten, Emmelien, Wilde, Arthur A A M, van den Wijngaard, Arthur, Broers, Jos L, Jongbloed, Jan D. H., van der Velden, Jolanda, van den Berg, Maarten P., van Tintelen, J. Peter, Hoorntje, Edgar T, Bollen, Ilse Ae, Barge-Schaapveld, Daniela Q, Van Tienen, Florence H J, Te Meerman, Gerard J, Jansweijer, Joeri A, van Essen, Anthonie J, Volders, Paul G. A., Constantinescu, Alina, Van Den Akker, Peter C., van Spaendonck-Zwarts, Karin Y., Oldenburg, Rogier A, Marcelis, Carlo L. M., van der Smagt, Jasper J, Hennekam, Eric A, Vink, Aryan, Bootsma, Marianne, Aten, Emmelien, Wilde, Arthur A A M, van den Wijngaard, Arthur, Broers, Jos L, Jongbloed, Jan D. H., van der Velden, Jolanda, van den Berg, Maarten P., and van Tintelen, J. Peter

Published
2017

8. Lamin A/C-Related Cardiac Disease : Late Onset With a Variable and Mild Phenotype in a Large Cohort of Patients With the Lamin A/C p.(Arg331Gln) Founder Mutation

Author

Hoorntje, Edgar T, Bollen, Ilse Ae, Barge-Schaapveld, Daniela Q, Van Tienen, Florence H J, Te Meerman, Gerard J, Jansweijer, Joeri A, van Essen, Anthonie J, Volders, Paul G. A., Constantinescu, Alina, Van Den Akker, Peter C., van Spaendonck-Zwarts, Karin Y., Oldenburg, Rogier A, Marcelis, Carlo L. M., van der Smagt, Jasper J, Hennekam, Eric A, Vink, Aryan, Bootsma, Marianne, Aten, Emmelien, Wilde, Arthur A A M, van den Wijngaard, Arthur, Broers, Jos L, Jongbloed, Jan D. H., van der Velden, Jolanda, van den Berg, Maarten P., van Tintelen, J. Peter, Hoorntje, Edgar T, Bollen, Ilse Ae, Barge-Schaapveld, Daniela Q, Van Tienen, Florence H J, Te Meerman, Gerard J, Jansweijer, Joeri A, van Essen, Anthonie J, Volders, Paul G. A., Constantinescu, Alina, Van Den Akker, Peter C., van Spaendonck-Zwarts, Karin Y., Oldenburg, Rogier A, Marcelis, Carlo L. M., van der Smagt, Jasper J, Hennekam, Eric A, Vink, Aryan, Bootsma, Marianne, Aten, Emmelien, Wilde, Arthur A A M, van den Wijngaard, Arthur, Broers, Jos L, Jongbloed, Jan D. H., van der Velden, Jolanda, van den Berg, Maarten P., and van Tintelen, J. Peter

Published
2017

9. Lamin A/C-Related Cardiac Disease : Late Onset With a Variable and Mild Phenotype in a Large Cohort of Patients With the Lamin A/C p.(Arg331Gln) Founder Mutation

Author

Hoorntje, Edgar T, Bollen, Ilse Ae, Barge-Schaapveld, Daniela Q, Van Tienen, Florence H J, Te Meerman, Gerard J, Jansweijer, Joeri A, van Essen, Anthonie J, Volders, Paul G. A., Constantinescu, Alina, Van Den Akker, Peter C., van Spaendonck-Zwarts, Karin Y., Oldenburg, Rogier A, Marcelis, Carlo L. M., van der Smagt, Jasper J, Hennekam, Eric A, Vink, Aryan, Bootsma, Marianne, Aten, Emmelien, Wilde, Arthur A A M, van den Wijngaard, Arthur, Broers, Jos L, Jongbloed, Jan D. H., van der Velden, Jolanda, van den Berg, Maarten P., van Tintelen, J. Peter, Hoorntje, Edgar T, Bollen, Ilse Ae, Barge-Schaapveld, Daniela Q, Van Tienen, Florence H J, Te Meerman, Gerard J, Jansweijer, Joeri A, van Essen, Anthonie J, Volders, Paul G. A., Constantinescu, Alina, Van Den Akker, Peter C., van Spaendonck-Zwarts, Karin Y., Oldenburg, Rogier A, Marcelis, Carlo L. M., van der Smagt, Jasper J, Hennekam, Eric A, Vink, Aryan, Bootsma, Marianne, Aten, Emmelien, Wilde, Arthur A A M, van den Wijngaard, Arthur, Broers, Jos L, Jongbloed, Jan D. H., van der Velden, Jolanda, van den Berg, Maarten P., and van Tintelen, J. Peter

Published
2017

10. Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases.

Author

Stessman, Holly AF, Stessman, Holly AF, Xiong, Bo, Coe, Bradley P, Wang, Tianyun, Hoekzema, Kendra, Fenckova, Michaela, Kvarnung, Malin, Gerdts, Jennifer, Trinh, Sandy, Cosemans, Nele, Vives, Laura, Lin, Janice, Turner, Tychele N, Santen, Gijs, Ruivenkamp, Claudia, Kriek, Marjolein, van Haeringen, Arie, Aten, Emmelien, Friend, Kathryn, Liebelt, Jan, Barnett, Christopher, Haan, Eric, Shaw, Marie, Gecz, Jozef, Anderlid, Britt-Marie, Nordgren, Ann, Lindstrand, Anna, Schwartz, Charles, Kooy, R Frank, Vandeweyer, Geert, Helsmoortel, Celine, Romano, Corrado, Alberti, Antonino, Vinci, Mirella, Avola, Emanuela, Giusto, Stefania, Courchesne, Eric, Pramparo, Tiziano, Pierce, Karen, Nalabolu, Srinivasa, Amaral, David G, Scheffer, Ingrid E, Delatycki, Martin B, Lockhart, Paul J, Hormozdiari, Fereydoun, Harich, Benjamin, Castells-Nobau, Anna, Xia, Kun, Peeters, Hilde, Nordenskjöld, Magnus, Schenck, Annette, Bernier, Raphael A, Eichler, Evan E, Stessman, Holly AF, Stessman, Holly AF, Xiong, Bo, Coe, Bradley P, Wang, Tianyun, Hoekzema, Kendra, Fenckova, Michaela, Kvarnung, Malin, Gerdts, Jennifer, Trinh, Sandy, Cosemans, Nele, Vives, Laura, Lin, Janice, Turner, Tychele N, Santen, Gijs, Ruivenkamp, Claudia, Kriek, Marjolein, van Haeringen, Arie, Aten, Emmelien, Friend, Kathryn, Liebelt, Jan, Barnett, Christopher, Haan, Eric, Shaw, Marie, Gecz, Jozef, Anderlid, Britt-Marie, Nordgren, Ann, Lindstrand, Anna, Schwartz, Charles, Kooy, R Frank, Vandeweyer, Geert, Helsmoortel, Celine, Romano, Corrado, Alberti, Antonino, Vinci, Mirella, Avola, Emanuela, Giusto, Stefania, Courchesne, Eric, Pramparo, Tiziano, Pierce, Karen, Nalabolu, Srinivasa, Amaral, David G, Scheffer, Ingrid E, Delatycki, Martin B, Lockhart, Paul J, Hormozdiari, Fereydoun, Harich, Benjamin, Castells-Nobau, Anna, Xia, Kun, Peeters, Hilde, Nordenskjöld, Magnus, Schenck, Annette, Bernier, Raphael A, and Eichler, Evan E

Abstract

Gene-disruptive mutations contribute to the biology of neurodevelopmental disorders (NDDs), but most of the related pathogenic genes are not known. We sequenced 208 candidate genes from >11,730 cases and >2,867 controls. We identified 91 genes, including 38 new NDD genes, with an excess of de novo mutations or private disruptive mutations in 5.7% of cases. Drosophila functional assays revealed a subset with increased involvement in NDDs. We identified 25 genes showing a bias for autism versus intellectual disability and highlighted a network associated with high-functioning autism (full-scale IQ >100). Clinical follow-up for NAA15, KMT5B, and ASH1L highlighted new syndromic and nonsyndromic forms of disease.

Published
2017

11. Lamin A/C-Related Cardiac Disease: Late Onset With a Variable and Mild Phenotype in a Large Cohort of Patients With the Lamin A/C p.(Arg331Gln) Founder Mutation

Author

Genetica Klinische Genetica, Circulatory Health, Pathologie Pathologen staf, Hoorntje, Edgar T, Bollen, Ilse Ae, Barge-Schaapveld, Daniela Q, Van Tienen, Florence H J, Te Meerman, Gerard J, Jansweijer, Joeri A, van Essen, Anthonie J, Volders, Paul G. A., Constantinescu, Alina, Van Den Akker, Peter C., van Spaendonck-Zwarts, Karin Y., Oldenburg, Rogier A, Marcelis, Carlo L. M., van der Smagt, Jasper J, Hennekam, Eric A, Vink, Aryan, Bootsma, Marianne, Aten, Emmelien, Wilde, Arthur A A M, van den Wijngaard, Arthur, Broers, Jos L, Jongbloed, Jan D. H., van der Velden, Jolanda, van den Berg, Maarten P., van Tintelen, J. Peter, Genetica Klinische Genetica, Circulatory Health, Pathologie Pathologen staf, Hoorntje, Edgar T, Bollen, Ilse Ae, Barge-Schaapveld, Daniela Q, Van Tienen, Florence H J, Te Meerman, Gerard J, Jansweijer, Joeri A, van Essen, Anthonie J, Volders, Paul G. A., Constantinescu, Alina, Van Den Akker, Peter C., van Spaendonck-Zwarts, Karin Y., Oldenburg, Rogier A, Marcelis, Carlo L. M., van der Smagt, Jasper J, Hennekam, Eric A, Vink, Aryan, Bootsma, Marianne, Aten, Emmelien, Wilde, Arthur A A M, van den Wijngaard, Arthur, Broers, Jos L, Jongbloed, Jan D. H., van der Velden, Jolanda, van den Berg, Maarten P., and van Tintelen, J. Peter

Published
2017

12. Structural genomic variation in childhood epilepsies with complex phenotypes

Author

Helbig, Ingo, Swinkels, Marielle E M, Aten, Emmelien, Caliebe, Almuth, van 't Slot, Ruben, Boor, Rainer, von Spiczak, Sarah, Muhle, Hiltrud, Jähn, Johanna A, van Binsbergen, Ellen, van Nieuwenhuizen, Onno, Jansen, Floor E, Braun, Kees P J, de Haan, Gerrit-Jan, Tommerup, Niels, Stephani, Ulrich, Hjalgrim, Helle, Poot, Martin, Lindhout, Dick, Brilstra, Eva H, Møller, Rikke S, Koeleman, Bobby P C, Helbig, Ingo, Swinkels, Marielle E M, Aten, Emmelien, Caliebe, Almuth, van 't Slot, Ruben, Boor, Rainer, von Spiczak, Sarah, Muhle, Hiltrud, Jähn, Johanna A, van Binsbergen, Ellen, van Nieuwenhuizen, Onno, Jansen, Floor E, Braun, Kees P J, de Haan, Gerrit-Jan, Tommerup, Niels, Stephani, Ulrich, Hjalgrim, Helle, Poot, Martin, Lindhout, Dick, Brilstra, Eva H, Møller, Rikke S, and Koeleman, Bobby P C

Abstract

A genetic contribution to a broad range of epilepsies has been postulated, and particularly copy number variations (CNVs) have emerged as significant genetic risk factors. However, the role of CNVs in patients with epilepsies with complex phenotypes is not known. Therefore, we investigated the role of CNVs in patients with unclassified epilepsies and complex phenotypes. A total of 222 patients from three European countries, including patients with structural lesions on magnetic resonance imaging (MRI), dysmorphic features, and multiple congenital anomalies, were clinically evaluated and screened for CNVs. MRI findings including acquired or developmental lesions and patient characteristics were subdivided and analyzed in subgroups. MRI data were available for 88.3% of patients, of whom 41.6% had abnormal MRI findings. Eighty-eight rare CNVs were discovered in 71 out of 222 patients (31.9%). Segregation of all identified variants could be assessed in 42 patients, 11 of which were de novo. The frequency of all structural variants and de novo variants was not statistically different between patients with or without MRI abnormalities or MRI subcategories. Patients with dysmorphic features were more likely to carry a rare CNV. Genome-wide screening methods for rare CNVs may provide clues for the genetic etiology in patients with a broader range of epilepsies than previously anticipated, including in patients with various brain anomalies detectable by MRI. Performing genome-wide screens for rare CNVs can be a valuable contribution to the routine diagnostic workup in patients with a broad range of childhood epilepsies.

Published
2014

13. Structural genomic variation in childhood epilepsies with complex phenotypes

Author

Helbig, Ingo, Swinkels, Marielle E M, Aten, Emmelien, Caliebe, Almuth, van 't Slot, Ruben, Boor, Rainer, von Spiczak, Sarah, Muhle, Hiltrud, Jähn, Johanna A, van Binsbergen, Ellen, van Nieuwenhuizen, Onno, Jansen, Floor E, Braun, Kees P J, de Haan, Gerrit-Jan, Tommerup, Niels, Stephani, Ulrich, Hjalgrim, Helle, Poot, Martin, Lindhout, Dick, Brilstra, Eva H, Møller, Rikke S, Koeleman, Bobby P C, Helbig, Ingo, Swinkels, Marielle E M, Aten, Emmelien, Caliebe, Almuth, van 't Slot, Ruben, Boor, Rainer, von Spiczak, Sarah, Muhle, Hiltrud, Jähn, Johanna A, van Binsbergen, Ellen, van Nieuwenhuizen, Onno, Jansen, Floor E, Braun, Kees P J, de Haan, Gerrit-Jan, Tommerup, Niels, Stephani, Ulrich, Hjalgrim, Helle, Poot, Martin, Lindhout, Dick, Brilstra, Eva H, Møller, Rikke S, and Koeleman, Bobby P C

Abstract

A genetic contribution to a broad range of epilepsies has been postulated, and particularly copy number variations (CNVs) have emerged as significant genetic risk factors. However, the role of CNVs in patients with epilepsies with complex phenotypes is not known. Therefore, we investigated the role of CNVs in patients with unclassified epilepsies and complex phenotypes. A total of 222 patients from three European countries, including patients with structural lesions on magnetic resonance imaging (MRI), dysmorphic features, and multiple congenital anomalies, were clinically evaluated and screened for CNVs. MRI findings including acquired or developmental lesions and patient characteristics were subdivided and analyzed in subgroups. MRI data were available for 88.3% of patients, of whom 41.6% had abnormal MRI findings. Eighty-eight rare CNVs were discovered in 71 out of 222 patients (31.9%). Segregation of all identified variants could be assessed in 42 patients, 11 of which were de novo. The frequency of all structural variants and de novo variants was not statistically different between patients with or without MRI abnormalities or MRI subcategories. Patients with dysmorphic features were more likely to carry a rare CNV. Genome-wide screening methods for rare CNVs may provide clues for the genetic etiology in patients with a broader range of epilepsies than previously anticipated, including in patients with various brain anomalies detectable by MRI. Performing genome-wide screens for rare CNVs can be a valuable contribution to the routine diagnostic workup in patients with a broad range of childhood epilepsies.

Published
2014

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