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.
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Acknowledgements
We thank the participating families for their kind cooperation. This work was supported in part by fellowship grants by the LCRC from Osteogenesis Imperfecta Foundation (SNSC), DK081735-01A1, NIH/NIGMS T32 contract grant number GM07526 (AE). We thank Pengfei Lui for his input on the mechanism of rearrangement.
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Nagamani, S., Erez, A., Bader, P. et al. Phenotypic manifestations of copy number variation in chromosome 16p13.11. Eur J Hum Genet 19, 280–286 (2011). https://doi.org/10.1038/ejhg.2010.184
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DOI: https://doi.org/10.1038/ejhg.2010.184
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