Journal article
Rare copy number variants implicated in posterior urethral valves
American journal of medical genetics. Part A, Vol.170(3), pp.622-633
03/2016
DOI: 10.1002/ajmg.a.37493
PMCID: PMC6205289
PMID: 26663319
Abstract
The cause of posterior urethral valves (PUV) is unknown, but genetic factors are suspected given their familial occurrence. We examined cases of isolated PUV to identify novel copy number variants (CNVs). We identified 56 cases of isolated PUV from all live-births in New York State (1998-2005). Samples were genotyped using Illumina HumanOmni2.5 microarrays. Autosomal and sex-linked CNVs were identified using PennCNV and cnvPartition software. CNVs were prioritized for follow-up if they were absent from in-house controls, contained ≥ 10 consecutive probes, were ≥ 20 Kb in size, had ≤ 20% overlap with variants detected in other birth defect phenotypes screened in our lab, and were rare in population reference controls. We identified 47 rare candidate PUV-associated CNVs in 32 cases; one case had a 3.9 Mb deletion encompassing BMP7. Mutations in BMP7 have been associated with severe anomalies in the mouse urethra. Other interesting CNVs, each detected in a single PUV case included: a deletion of PIK3R3 and TSPAN1, duplication/triplication in FGF12, duplication of FAT1--a gene essential for normal growth and development, a large deletion (>2 Mb) on chromosome 17q that involves TBX2 and TBX4, and large duplications (>1 Mb) on chromosomes 3q and 6q. Our finding of previously unreported novel CNVs in PUV suggests that genetic factors may play a larger role than previously understood. Our data show a potential role of CNVs in up to 57% of cases examined. Investigation of genes in these CNVs may provide further insights into genetic variants that contribute to PUV.
Details
- Title: Subtitle
- Rare copy number variants implicated in posterior urethral valves
- Creators
- Nansi S Boghossian - Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MarylandRobert J Sicko - Department of Health, Division of Genetics, Wadsworth Center, Albany, New YorkDenise M Kay - Department of Health, Division of Genetics, Wadsworth Center, Albany, New YorkShannon L Rigler - Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MarylandMichele Caggana - Department of Health, Division of Genetics, Wadsworth Center, Albany, New YorkMichael Y Tsai - Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MinnesotaEdwina H Yeung - Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MarylandNathan Pankratz - Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MinnesotaBenjamin R Cole - Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MinnesotaCharlotte M Druschel - University at Albany School of Public Health, Rensselaer, New YorkPaul A Romitti - Department of Epidemiology, College of Public Health, The University of Iowa, Iowa City, IowaMarilyn L Browne - University at Albany School of Public Health, Rensselaer, New YorkRuzong Fan - Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MarylandAiyi Liu - Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MarylandLawrence C Brody - Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MarylandJames 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.170(3), pp.622-633
- Publisher
- United States
- DOI
- 10.1002/ajmg.a.37493
- PMID
- 26663319
- PMCID
- PMC6205289
- ISSN
- 1552-4825
- eISSN
- 1552-4833
- Grant note
- R01 DA024411 / NIDA NIH HHS Intramural NIH HHS Wellcome Trust HHSN275201100001C / NICHD NIH HHS HHSN275201100001I / NICHD NIH HHS HHSN27500005 / PHS HHS R01 DA012995 / NIDA NIH HHS HHSN275201100001G / NICHD NIH HHS N01-DK-73431 / NIDDK NIH HHS U01 DD001035 / NCBDD CDC HHS N01DK73431 / NICHD NIH HHS
- Language
- English
- Date published
- 03/2016
- Academic Unit
- Epidemiology; Biostatistics
- Record Identifier
- 9983995164602771
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