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dc.contributor.authorOzantürk, Ayşegül
dc.contributor.authorDavis, Erica E.
dc.contributor.authorSabo, Aniko
dc.contributor.authorWeiss, Marjan M.
dc.contributor.authorMuzny, Donna
dc.contributor.authorDugan-Perez, Shannon
dc.contributor.authorSistermans, Erik A.
dc.contributor.authorGibbs, Richard A.
dc.contributor.authorÖzgül, Köksal R.
dc.contributor.authorYalnızoglu, Dilek
dc.contributor.authorSerdaroglu, Esra
dc.contributor.authorDursun, Ali
dc.contributor.authorKatsanis, Nicholas
dc.date.accessioned2019-12-10T10:42:37Z
dc.date.available2019-12-10T10:42:37Z
dc.date.issued2016
dc.identifier.issn2373-2865
dc.identifier.urihttps://doi.org/10.1101/mcs.a000703
dc.identifier.urihttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4849851/
dc.identifier.urihttp://hdl.handle.net/11655/14246
dc.description.abstractGenetic studies grounded on monogenic paradigms have accelerated both gene discovery and molecular diagnosis. At the same time, complex genomic rearrangements are also appreciated as potent drivers of disease pathology. Here, we report two male siblings with a dysmorphic face, ambiguous genitalia, intellectual disability, and speech delay. Through quad-based whole-exome sequencing and concomitant molecular cytogenetic testing, we identified two copy-number variants (CNVs) in both affected individuals likely arising from a balanced translocation: a 13.5-Mb duplication on Chromosome 16 (16q23.1 → 16qter) and a 7.7-Mb deletion on Chromosome 5 (5p15.31 → 5pter), as well as a hemizygous missense variant in CXorf36 (also known as DIA1R). The 5p terminal deletion has been associated previously with speech delay, whereas craniofacial dysmorphia and genital/urinary anomalies have been reported in patients with a terminal duplication of 16q. However, dosage changes in either genomic region alone could not account for the overall clinical presentation in our family; functional testing of CXorf36 in zebrafish did not induce defects in neurogenesis or the craniofacial skeleton. Notably, literature and database analysis revealed a similar dosage disruption in two siblings with extensive phenotypic overlap with our patients. Taken together, our data suggest that dosage perturbation of genes within the two chromosomal regions likely drives the syndromic manifestations of our patients and highlight how multiple genetic lesions can contribute to complex clinical pathologies.
dc.relation.isversionof10.1101/mcs.a000703
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleA T(5;16) Translocation Is The Likely Driver Of A Syndrome With Ambiguous Genitalia, Facial Dysmorphism, Intellectual Disability, And Speech Delay
dc.typeinfo:eu-repo/semantics/article
dc.relation.journalCold Spring Harbor Molecular Case Studies
dc.contributor.departmentÇocuk Sağlığı ve Hastalıkları
dc.identifier.volume2
dc.identifier.issue2
dc.description.indexPubMed


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