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De novo mutations in ARID1B associated with both syndromic and non-syndromic short stature.
- Source :
-
BMC genomics [BMC Genomics] 2015 Sep 16; Vol. 16, pp. 701. Date of Electronic Publication: 2015 Sep 16. - Publication Year :
- 2015
-
Abstract
- Background: Human height is a complex trait with a strong genetic basis. Recently, a significant association between rare copy number variations (CNVs) and short stature has been identified, and candidate genes in these rare CNVs are being explored. This study aims to evaluate the association between mutations in ARID1B gene and short stature, both the syndromic and non-syndromic form.<br />Results: Based on a case-control study of whole genome chromosome microarray analysis (CMA), three overlapping CNVs were identified in patients with developmental disorders who exhibited short stature. ARID1B, a causal gene for Coffin Siris syndrome, is the only gene encompassed by all three CNVs. A following retrospective genotype-phenotype analysis based on a literature review confirmed that short stature is a frequent feature in those Coffin-Siris syndrome patients with ARID1B mutations. Mutation screening of ARID1B coding regions was further conducted in a cohort of 48 non-syndromic short stature patients,andfour novel missense variants including two de novo mutations were found.<br />Conclusion: These results suggest that haploinsufficient mutations of ARID1B are associated with syndromic short stature including Coffin-Siris syndrome and intellectual disability, while rare missense variants in ARID1B are associated with non-syndromic short stature. This study supports the notion that mutations in genes related to syndromic short stature may exert milder effect and contribute to short stature in the general population.
- Subjects :
- Abnormalities, Multiple
Adolescent
Case-Control Studies
Chromosomes, Human, Pair 6 genetics
DNA Copy Number Variations
DNA Mutational Analysis
Developmental Disabilities genetics
Face abnormalities
Female
Genome-Wide Association Study
Hand Deformities, Congenital
Humans
Intellectual Disability
Male
Micrognathism
Neck abnormalities
Retrospective Studies
Sequence Deletion
DNA-Binding Proteins genetics
Dwarfism genetics
Genetic Association Studies
Mutation
Transcription Factors genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1471-2164
- Volume :
- 16
- Database :
- MEDLINE
- Journal :
- BMC genomics
- Publication Type :
- Academic Journal
- Accession number :
- 26376624
- Full Text :
- https://doi.org/10.1186/s12864-015-1898-1