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Alternative genomic diagnoses for individuals with a clinical diagnosis of Dubowitz syndrome

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dc.contributor.authorGEÇKİNLİ, BİLGEN BİLGE
dc.contributor.authorsDyment, 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
dc.date.accessioned2022-03-14T09:33:14Z
dc.date.available2022-03-14T09:33:14Z
dc.date.issued2021-01
dc.description.abstractDubowitz 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.
dc.identifier.doi10.1002/ajmg.a.61926
dc.identifier.eissn1552-4833
dc.identifier.issn1552-4825
dc.identifier.pubmed33098347
dc.identifier.urihttps://hdl.handle.net/11424/243257
dc.identifier.wosWOS:000581797000001
dc.language.isoeng
dc.publisherWILEY
dc.relation.ispartofAMERICAN JOURNAL OF MEDICAL GENETICS PART A
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectDubowitz syndrome
dc.subjectexome sequencing
dc.subjectgenetic heterogeneity
dc.subjectgenome sequencing
dc.subjectmicroarray
dc.subjectLOSS-OF-FUNCTION
dc.subjectINTELLECTUAL DISABILITY
dc.subjectMUTATIONS
dc.subjectANEMIA
dc.subjectNSUN2
dc.subjectFRAMESHIFT
dc.subjectPHENOTYPE
dc.subjectANOMALIES
dc.subjectPLATFORM
dc.subjectPATIENT
dc.titleAlternative genomic diagnoses for individuals with a clinical diagnosis of Dubowitz syndrome
dc.typearticle
dspace.entity.typePublication
local.avesis.idf37b3db1-a420-4fa3-8654-6bbe485d6745
local.import.packageSS16
local.indexed.atWOS
local.indexed.atSCOPUS
local.indexed.atPUBMED
local.journal.numberofpages15
local.journal.quartileQ3
oaire.citation.endPage133
oaire.citation.issue1
oaire.citation.startPage119
oaire.citation.titleAMERICAN JOURNAL OF MEDICAL GENETICS PART A
oaire.citation.volume185
relation.isAuthorOfPublication5f812a34-2d87-4040-b76f-0b90c1c695ae
relation.isAuthorOfPublication.latestForDiscovery5f812a34-2d87-4040-b76f-0b90c1c695ae

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