A t(5;16) translocation is the likely driver of a syndrome with ambiguous genitalia, facial dysmorphism, intellectual disability, and speech delay

• DOI: 10.1101/mcs.a000703
• Publication Date: 2016-02-15T18:35:55Z
• Authors: Ayşegül Ozantürk; Erica E. Davis; Aniko Sabo; Marjan M. Weiss; Donna Muzny; Shannon Dugan-Perez; Erik A. Sistermans; Richard A. Gibbs; Köksal R. Özgül; Dilek Yalnızoglu; Esra Serdaroglu; Ali Dursun; Nicholas Katsanis
• Keywords: Comparative genomic hybridization; Exome; Chromosomal rearrangement

Genetic 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, speech delay. Through quad-based whole-exome sequencing concomitant cytogenetic testing, identified copy-number variants (CNVs) in affected individuals likely arising from balanced translocation: 13.5-Mb duplication Chromosome 16 (16q23.1 → 16qter) 7.7-Mb deletion 5 (5p15.31 5pter), well hemizygous missense variant CXorf36 (also known DIA1R). The 5p terminal has been associated previously delay, whereas craniofacial dysmorphia genital/urinary anomalies reported patients 16q. However, dosage changes either region alone could not account for overall clinical presentation our family; functional testing zebrafish did induce defects neurogenesis or skeleton. Notably, literature database analysis revealed similar disruption extensive phenotypic overlap patients. Taken together, data suggest that perturbation genes within chromosomal regions drives syndromic manifestations highlight how multiple genetic lesions can contribute to pathologies.