%0 Journal Article %J Am J Med Genet A %D 2021 %T Alternative genomic diagnoses for individuals with a clinical diagnosis of Dubowitz syndrome. %A Dyment, David A %A O'Donnell-Luria, Anne %A Agrawal, Pankaj B %A Coban Akdemir, Zeynep %A Aleck, Kyrieckos A %A Antaki, Danny %A Al Sharhan, Hind %A Au, Ping-Yee B %A Aydin, Hatip %A Beggs, Alan H %A Bilguvar, Kaya %A Eric Boerwinkle %A Brand, Harrison %A Brownstein, Catherine A %A Buyske, Steve %A Chodirker, Bernard %A Choi, Jungmin %A Chudley, Albert E %A Clericuzio, Carol L %A Cox, Gerald F %A Curry, Cynthia %A de Boer, Elke %A de Vries, Bert B A %A Dunn, Kathryn %A Dutmer, Cullen M %A England, Eleina M %A Fahrner, Jill A %A Geckinli, Bilgen B %A Genetti, Casie A %A Gezdirici, Alper %A Gibson, William T %A Gleeson, Joseph G %A Greenberg, Cheryl R %A Hall, April %A Hamosh, Ada %A Hartley, Taila %A Jhangiani, Shalini N %A Karaca, Ender %A Kernohan, Kristin %A Lauzon, Julie L %A Lewis, M E Suzanne %A Lowry, R Brian %A López-Giráldez, Francesc %A Matise, Tara C %A McEvoy-Venneri, Jennifer %A McInnes, Brenda %A Mhanni, Aziz %A Garcia Minaur, Sixto %A Moilanen, Jukka %A Nguyen, An %A Nowaczyk, Malgorzata J M %A Posey, Jennifer E %A Õunap, Katrin %A Pehlivan, Davut %A Pajusalu, Sander %A Penney, Lynette S %A Poterba, Timothy %A Prontera, Paolo %A Doriqui, Maria Juliana Rodovalho %A Sawyer, Sarah L %A Sobreira, Nara %A Stanley, Valentina %A Torun, Deniz %A Wargowski, David %A Witmer, P Dane %A Wong, Isaac %A Xing, Jinchuan %A Zaki, Maha S %A Zhang, Yeting %A Boycott, Kym M %A Bamshad, Michael J %A Nickerson, Deborah A %A Blue, Elizabeth E %A Innes, A Micheil %K Adolescent %K Child %K Child, Preschool %K DNA Copy Number Variations %K Eczema %K Exome %K Exome Sequencing %K Facies %K Female %K Genetic Predisposition to Disease %K Genome, Human %K Genomics %K Growth Disorders %K Histone Deacetylases %K Humans %K Infant %K Intellectual Disability %K Male %K Microcephaly %K Phenotype %K Repressor Proteins %X

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.

%B Am J Med Genet A %V 185 %P 119-133 %8 2021 Jan %G eng %N 1 %1 https://www.ncbi.nlm.nih.gov/pubmed/33098347?dopt=Abstract %R 10.1002/ajmg.a.61926