PUBLICATION
A t(5;16) translocation is the likely driver of a syndrome with ambiguous genitalia, facial dysmorphism, intellectual disability, and speech delay
- Authors
- Ozantürk, A., Davis, E.E., Sabo, A., Weiss, M.M., Muzny, D., Dugan-Perez, S., Sistermans, E.A., Gibbs, R.A., Özgül, K.R., Yalnızoglu, D., Serdaroglu, E., Dursun, A., Katsanis, N.
- ID
- ZDB-PUB-160506-4
- Date
- 2016
- Source
- Cold Spring Harbor molecular case studies 2: a000703 (Journal)
- Registered Authors
- Davis, Erica, Katsanis, Nicholas
- Keywords
- cat cry, central hypotonia, clubbing of toes, delayed gross motor development, down-sloping shoulders, enlarged proximal interphalangeal joints, high, narrow palate, intellectual disability, profound, micropenis, moderately short stature, penile hypospadias, pes planus, prominent forehead, thin upper lip vermilion, wide nasal bridge
- MeSH Terms
- none
- PubMed
- 27148584 Full text @ Cold Spring Harb Mol Case Stud
Citation
Ozantürk, A., Davis, E.E., Sabo, A., Weiss, M.M., Muzny, D., Dugan-Perez, S., Sistermans, E.A., Gibbs, R.A., Özgül, K.R., Yalnızoglu, D., Serdaroglu, E., Dursun, A., Katsanis, N. (2016) A t(5;16) translocation is the likely driver of a syndrome with ambiguous genitalia, facial dysmorphism, intellectual disability, and speech delay. Cold Spring Harbor molecular case studies. 2:a000703.
Abstract
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, 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping