Alternative genomic diagnoses for individuals with a clinical diagnosis of Dubowitz syndrome
- Authors
- Dyment, David A.; O'Donnell-Luria, Anne; Agrawal, Pankaj B.; Coban Akdemir, Zeynep; Aleck, Kyrieckos A.; Antaki, Danny; Al Sharhan, Hind; Au, Ping-Yee B.; Aydin, Hatip; Beggs, Alan H.; Bilguvar, Kaya; Boerwinkle, Eric; Brand, Harrison; Brownstein, Catherine A.; Buyske, Steve; Chodirker, Bernard; Choi, Jungmin; Chudley, Albert E.; Clericuzio, Carol L.; Cox, Gerald F.; Curry, Cynthia; de Boer, Elke; de Vries, Bert B. A.; Dunn, Kathryn; Dutmer, Cullen M.; England, Eleina M.; Fahrner, Jill A.; Geckinli, Bilgen B.; Genetti, Casie A.; Gezdirici, Alper; Gibson, William T.; Gleeson, Joseph G.; Greenberg, Cheryl R.; Hall, April; Hamosh, Ada; Hartley, Taila; Jhangiani, Shalini N.; Karaca, Ender; Kernohan, Kristin; Lauzon, Julie L.; Lewis, M. E. Suzanne; Lowry, R. Brian; Lopez-Giraldez, Francesc; Matise, Tara C.; McEvoy-Venneri, Jennifer; McInnes, Brenda; Mhanni, Aziz; Garcia Minaur, Sixto; Moilanen, Jukka; Nguyen, An; Nowaczyk, Malgorzata J. M.; Posey, Jennifer E.; Ounap, Katrin; Pehlivan, Davut; Pajusalu, Sander; Penney, Lynette S.; Poterba, Timothy; Prontera, Paolo; Doriqui, Maria Juliana Rodovalho; Sawyer, Sarah L.; Sobreira, Nara; Stanley, Valentina; Torun, Deniz; Wargowski, David; Witmer, P. Dane; Wong, Isaac; Xing, Jinchuan; Zaki, Maha S.; Zhang, Yeting; Boycott, Kym M.; Bamshad, Michael J.; Nickerson, Deborah A.; Blue, Elizabeth E.; Innes, A. Micheil
- Issue Date
- 1월-2021
- Publisher
- WILEY
- Keywords
- Dubowitz syndrome; exome sequencing; genetic heterogeneity; genome sequencing; microarray
- Citation
- AMERICAN JOURNAL OF MEDICAL GENETICS PART A, v.185, no.1, pp.119 - 133
- Indexed
- SCIE
SCOPUS
- Journal Title
- AMERICAN JOURNAL OF MEDICAL GENETICS PART A
- Volume
- 185
- Number
- 1
- Start Page
- 119
- End Page
- 133
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/129508
- DOI
- 10.1002/ajmg.a.61926
- ISSN
- 1552-4825
- Abstract
- Dubowitz syndrome (DubS) is considered a recognizable syndrome characterized by a distinctive facial appearance and deficits in growth and development. There have been over 200 individuals reported with Dubowitz or a "Dubowitz-like" condition, although no single gene has been implicated as responsible for its cause. We have performed exome (ES) or genome sequencing (GS) for 31 individuals clinically diagnosed with DubS. After genome-wide sequencing, rare variant filtering and computational and Mendelian genomic analyses, a presumptive molecular diagnosis was made in 13/27 (48%) families. The molecular diagnoses included biallelic variants in SKIV2L, SLC35C1, BRCA1, NSUN2; de novo variants in ARID1B, ARID1A, CREBBP, POGZ, TAF1, HDAC8, and copy-number variation at1p36.11(ARID1A), 8q22.2(VPS13B), Xp22, and Xq13(HDAC8). Variants of unknown significance in known disease genes, and also in genes of uncertain significance, were observed in 7/27 (26%) additional families. Only one gene, HDAC8, could explain the phenotype in more than one family (N = 2). All but two of the genomic diagnoses were for genes discovered, or for conditions recognized, since the introduction of next-generation sequencing. Overall, the DubS-like clinical phenotype is associated with extensive locus heterogeneity and the molecular diagnoses made are for emerging clinical conditions sharing characteristic features that overlap the DubS phenotype.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - Graduate School > Department of Biomedical Sciences > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.