Phenotypic manifestations of copy number variation in chromosome 16p13.11

Abstract

The widespread clinical utilization of array comparative genome hybridization, has led to the unraveling of many new copy number variations (CNVs). Although some of these CNVs are clearly pathogenic, the phenotypic consequences of others, such as those in 16p13.11 remain unclear. Whereas deletions of 16p13.11 have been associated with multiple congenital anomalies, the relevance of duplications of the region is still being debated. We report detailed clinical and molecular characterization of 10 patients with duplication and 4 patients with deletion of 16p13.11. We found that patients with duplication of the region have varied clinical features including behavioral abnormalities, cognitive impairment, congenital heart defects and skeletal manifestations, such as hypermobility, craniosynostosis and polydactyly. These features were incompletely penetrant. Patients with deletion of the region presented with microcephaly, developmental delay and behavioral abnormalities as previously described. The CNVs were of varying sizes and were likely mediated by non-allelic homologous recombination between low copy repeats. Our findings expand the repertoire of clinical features observed in patients with CNV in 16p13.11 and strengthen the hypothesis that this is a dosage sensitive region with clinical relevance.

Application of custom-designed oligonucleotide array CGH in 145 patients with autistic spectrum disorders

“…30 However, other reports associated this CNV with a variety of neuropsychiatric and neurobehavioral disorders, including autism, schizophrenia, intellectual disabilities, cognitive impairment, attention deficit hyperactivity disorder, and epilepsy, as well as congenital heart defects, skeletal manifestations, and thoracic aortic aneurysms and dissections. [31][32][33][34][35][36][37] We suggest that this duplication may contribute to the autistic features seen in patient 7.…”

Copy number analysis of 413 isolated talipes equinovarus patients suggests role for transcriptional regulators of early limb development

“…40 We identified an enrichment of chromosome 16p13.1 CNVs (P ¼ 0.036), consisting of one deletion and three duplications in our isolated talipes equinovarus cohort and a single duplication in our bipolar controls. These patients are all developmentally normal and lack family history of aortic or neuropsychiatric disease.…”

Copy number variations in 375 patients with oesophageal atresia and/or tracheoesophageal fistula

“…Duplications of this region between the NOMO1 and XYLT1 gene have been described previously in patients with various phenotypical anomalies, including the OA/TOF-associated congenital anomalies and anal and cardiac malformations. 48 None of the other overlapping rare CNVs found in our cohort (see supplementary table 1) was enriched in the developmental delay study.…”