Copy number variants in a population-based investigation of Klippel-Trenaunay syndrome.
Am J Med Genet A
; 173(2): 352-359, 2017 Feb.
Article
in En
| MEDLINE
| ID: mdl-27901321
ABSTRACT
Klippel-Trenaunay syndrome (KTS) is a rare congenital vascular disorder that is thought to occur sporadically; however, reports of familial occurrence suggest a genetic component. We examined KTS cases to identify novel, potentially causal copy number variants (CNVs). We identified 17 KTS cases from all live-births occurring in New York (1998-2010). Extracted DNA was genotyped using Illumina microarrays and CNVs were called using PennCNV software. CNVs selected for follow-up had ≥10 single nucleotide polymorphisms (SNPs) and minimal overlap with in-house controls or controls from the Database of Genomic Variants. We identified 15 candidate CNVs in seven cases; among them a deletion in two cases within transcripts of HDAC9, a histone deacetylase essential for angiogenic sprouting of endothelial cells. One of them also had a duplication upstream of SALL3, a transcription factor essential for embryonic development that inhibits DNMT3A, a DNA methyltransferase responsible for embryonic de novo DNA methylation. Another case had a duplication spanning ING5, a histone acetylation regulator active during embryogenesis. We identified rare genetic variants related to chromatin modification which may have a key role in regulating vascular development during embryogenesis. Further investigation of their implications in the pathogenesis of KTS is warranted. © 2016 Wiley Periodicals, Inc.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Klippel-Trenaunay-Weber Syndrome
/
Genetic Association Studies
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DNA Copy Number Variations
Type of study:
Observational_studies
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Prevalence_studies
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Prognostic_studies
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Risk_factors_studies
/
Screening_studies
Limits:
Humans
Language:
En
Journal:
Am J Med Genet A
Journal subject:
GENETICA MEDICA
Year:
2017
Type:
Article