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https://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 |
DOI: | 10.1038/ng.534 |
Published version: | http://dx.doi.org/10.1038/ng.534 |
Appears in Collections: | Aurora harvest Paediatrics publications |
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