Copy Number Variants in a Population-Based Investigation of Klippel–Trenaunay Syndrome

Details

• Alternative Title:
  Am J Med Genet A
• Personal Author:
  Dimopoulos, Aggeliki ; Sicko, Robert J. ; Kay, Denise M. ; Rigler, Shannon L. ; Fan, Ruzong ; Romitti, Paul A. ; Browne, Marilyn L. ; Druschel, Charlotte M. ; Caggana, Michele ; Brody, Lawrence C. ; Mills, James L.
• Description:
  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.
• Subjects:
  Case-Control Studies Chromosome Mapping Comparative Genomic Hybridization DNA Copy Number Variations Genetic Association Studies Genetic Testing Genotype Histone Deacetylases Humans Klippel-Trenaunay-Weber Syndrome Maternal Age Polymorphism, Single Nucleotide Population Surveillance Prevalence Registries Repressor Proteins

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• Keywords:
  Angiogenesis Chromatin Modification Copy Number Variant DNMT3A HDAC9 ING5 Klippel–Trenaunay Syndrome SALL3
• Source:
  Am J Med Genet A. 173(2):352-359
• Pubmed ID:
  27901321
• Pubmed Central ID:
  PMC6205266
• Document Type:
  Journal Article
• Funding:
  WT_/Wellcome TrustUnited Kingdom/ ; HHSN275201100001I/HD/NICHD NIH HHSUnited States/ ; N01DK73431/HD/NICHD NIH HHSUnited States/ ; U01 DD001035/DD/NCBDD CDC HHSUnited States/
• Volume:
  173
• Issue:
  2
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:482b481b7fae988c5036093c2634bf7e6fdb3aafbdd17c2e533949cf03ac1bc6
• Download URL:
  https://stacks.cdc.gov/view/cdc/82847/cdc_82847_DS1.pdf
• File Type:
  [PDF - 632.10 KB ]