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

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; James L Mills

doi:10.1002/ajmg.a.37868

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

Journal article

Peer reviewed

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

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, …

American journal of medical genetics. Part A, Vol.173(2), pp.352-359

02/2017

DOI: 10.1002/ajmg.a.37868

PMCID: PMC6205266

PMID: 27901321

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https://www.ncbi.nlm.nih.gov/pmc/articles/6205266View

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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.

Registries

Klippel-Trenaunay-Weber Syndrome - genetics

Genetic Testing

Klippel-Trenaunay-Weber Syndrome - epidemiology

Prevalence

Genetic Association Studies

Histone Deacetylases - genetics

Humans

Klippel-Trenaunay-Weber Syndrome - diagnosis

Repressor Proteins - genetics

Genotype

Chromosome Mapping

Case-Control Studies

DNA Copy Number Variations

Maternal Age

Comparative Genomic Hybridization

Polymorphism, Single Nucleotide

Population Surveillance

Details

Title: Subtitle: Copy number variants in a population-based investigation of Klippel-Trenaunay syndrome
Creators: Aggeliki Dimopoulos - Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
Robert J Sicko - Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, New York
Denise M Kay - Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, New York
Shannon L Rigler - Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
Ruzong Fan - Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
Paul A Romitti - Department of Epidemiology, College of Public Health, The University of Iowa, Iowa City, Iowa
Marilyn L Browne - Department of Epidemiology and Biostatistics, University at Albany School of Public Health, Rensselaer, New York
Charlotte M Druschel - Department of Epidemiology and Biostatistics, University at Albany School of Public Health, Rensselaer, New York
Michele Caggana - Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, New York
Lawrence C Brody - Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
James L Mills - Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
Resource Type: Journal article
Publication Details: American journal of medical genetics. Part A, Vol.173(2), pp.352-359
DOI: 10.1002/ajmg.a.37868
PMID: 27901321
PMCID: PMC6205266
NLM abbreviation: Am J Med Genet A
ISSN: 1552-4825
eISSN: 1552-4833
Publisher: United States
Grant note: Wellcome Trust HHSN275201100001I / NICHD NIH HHS HHSN275201100001C / NICHD NIH HHS HHSN275201100001G / NICHD NIH HHS U01 DD001035 / NCBDD CDC HHS N01DK73431 / NICHD NIH HHS
Language: English
Date published: 02/2017
Academic Unit: Epidemiology; Biostatistics
Record Identifier: 9983995136502771

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