Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/60752
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Type: Journal article
Title: A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay
Author: Haan, E.
Gecz, J.
Citation: Nature Genetics, 2010; 42(3):203-210
Publisher: Nature Publishing Group
Issue Date: 2010
ISSN: 1061-4036
1546-1718
Statement of
Responsibility: 
Santhosh Girirajan... Eric Haan... Josef Gecz... et al.
Abstract: We report the identification of a recurrent, 520-kb 16p12.1 microdeletion associated with childhood developmental delay. The microdeletion was detected in 20 of 11,873 cases compared with 2 of 8,540 controls (P = 0.0009, OR = 7.2) and replicated in a second series of 22 of 9,254 cases compared with 6 of 6,299 controls (P = 0.028, OR = 2.5). Most deletions were inherited, with carrier parents likely to manifest neuropsychiatric phenotypes compared to non-carrier parents (P = 0.037, OR = 6). Probands were more likely to carry an additional large copy-number variant when compared to matched controls (10 of 42 cases, P = 5.7 × 10−5, OR = 6.6). The clinical features of individuals with two mutations were distinct from and/or more severe than those of individuals carrying only the co-occurring mutation. Our data support a two-hit model in which the 16p12.1 microdeletion both predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in association with other large deletions or duplications. Analysis of other microdeletions with variable expressivity indicates that this two-hit model might be more generally applicable to neuropsychiatric disease.
Keywords: Chromosomes, Human, Pair 16; Humans; Chromosome Deletion; Recurrence; Oligonucleotide Array Sequence Analysis; Severity of Illness Index; Case-Control Studies; Pedigree; Family; Developmental Disabilities; Gene Frequency; Phenotype; Polymorphism, Single Nucleotide; Models, Genetic; Adult; Child; Child, Preschool; Infant; Comparative Genomic Hybridization
Rights: © 2010 Nature America
RMID: 0020095071
DOI: 10.1038/ng.534
Appears in Collections:Paediatrics publications

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