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

• Published in: European journal of human genetics : EJHG Vol. 19; no. 3; pp. 280 - 286
• Main Authors: Nagamani, Sandesh C Sreenath, Erez, Ayelet, Bader, Patricia, Lalani, Seema R, Scott, Daryl A, Scaglia, Fernando, Plon, Sharon E, Tsai, Chun-Hui, Reimschisel, Tyler, Roeder, Elizabeth, Malphrus, Amy D, Eng, Patricia A, Hixson, Patricia M, Kang, Sung-Hae L, Stankiewicz, Pawel, Patel, Ankita, Cheung, Sau Wai
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.03.2011; Nature Publishing Group
• Subjects: 631/208/205; 631/208/2489/1381; Abnormalities, Multiple - genetics; Abnormalities, Multiple - pathology; Autism; Bioinformatics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Child; Chromosome 16; Chromosome Deletion; Chromosome Duplication; Chromosomes; Chromosomes, Human, Pair 16 - genetics; Clonal deletion; Cloning; Cognitive ability; Cohort Studies; Comparative Genomic Hybridization; Congenital defects; Congenital diseases; Copy number; Craniosynostosis; Cytogenetics; Developmental Disabilities - genetics; Developmental Disabilities - pathology; Female; Fundamental and applied biological sciences. Psychology; Gene Expression; General aspects. Genetic counseling; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Genomes; Homologous recombination; Human Genetics; Human subjects; Humans; Infant; Intellectual disabilities; Laboratories; Male; Medical genetics; Medical sciences; Medicine; Microcephaly - genetics; Microcephaly - pathology; Microencephaly; Molecular and cellular biology; Patients; Pediatrics; Phenotype; Polydactyly; Schizophrenia; Segmental Duplications, Genomic; Variation; United States > US; behavioral abnormality; 16p13.11; CNV; cognitive impairment; Phenotype; Cognitive disorder; Copy number; Variations; Chromosome; Genetics; Behavioral disorder
• ISSN: 1018-4813; 1476-5438; 1476-5438
• DOI: 10.1038/ejhg.2010.184

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.