title: 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.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Sandesh C Sreenath
authors.initials: SC
authors.lastname: Nagamani
authors.forename: Ayelet
authors.initials: A
authors.lastname: Erez
authors.forename: Patricia
authors.initials: P
authors.lastname: Bader
authors.forename: Seema R
authors.initials: SR
authors.lastname: Lalani
authors.forename: Daryl A
authors.initials: DA
authors.lastname: Scott
authors.forename: Fernando
authors.initials: F
authors.lastname: Scaglia
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Plon
authors.forename: Chun-Hui
authors.initials: CH
authors.lastname: Tsai
authors.forename: Tyler
authors.initials: T
authors.lastname: Reimschisel
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Roeder
authors.forename: Amy D
authors.initials: AD
authors.lastname: Malphrus
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Eng
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Hixson
authors.forename: Sung-Hae L
authors.initials: SH
authors.lastname: Kang
authors.forename: Pawel
authors.initials: P
authors.lastname: Stankiewicz
authors.forename: Ankita
authors.initials: A
authors.lastname: Patel
authors.forename: Sau Wai
authors.initials: SW
authors.lastname: Cheung
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics / Q000473:pathology; D002648:Child; D002872:Chromosome Deletion; D058674:Chromosome Duplication; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D015331:Cohort Studies; D055028:Comparative Genomic Hybridization; D002658:Developmental Disabilities / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008831:Microcephaly / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D056916:Segmental Duplications, Genomic