Copy number variants in a population-based investigation of Klippel-Trenaunay syndrome

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• 作者：Aggeliki Dimopoulos ; Robert J. Sicko ; Denise M. Kay ; Shannon L. Rigler ; Ruzong Fan ; Paul A. Romitti ; Marilyn L. Browne ; Charlotte M. Druschel ; Michele Caggana ; Lawrence C. Brody and James L. Mills
• 刊名：American Journal of Medical Genetics Part A
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：173
• 期：2
• 页码：352-359
• 全文大小：871K
• ISSN：1552-4833

文摘

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.