Journal article
Copy number variants in hypoplastic right heart syndrome
American journal of medical genetics. Part A, Vol.176(12), pp.2760-2767
12/2018
DOI: 10.1002/ajmg.a.40527
PMID: 30289599
Abstract
Hypoplastic right heart syndrome (HRHS) is a rare congenital defect characterized by underdeveloped and malformed structures of the right heart. Familial recurrence of HRHS indicates genetic factors contribute to its etiology. Our study investigates the presence of copy number variants (CNVs) in HRHS cases. We genotyped 42 HRHS cases identified from live births throughout California (2003-2010) using the Illumina HumanOmni2.5-8 array. We identified 14 candidate CNVs in 14 HRHS cases (33%) based on the genes included in the CNVs and their functions. Duplications overlapping part of ERBB4 were identified in two unrelated cases. ERBB4 is a neuregulin receptor with a pivotal role in cardiomyocyte differentiation and heart development. We also described a 7.5 Mb duplication at 16q11-12. Multiple genes in the duplicated region have previously been linked to heart defects and cardiac development, including RPGRIP1L, RBL2, SALL1, and MYLK3. Of the 14 validated CNVs, we identified four CNVs in close proximity to genes linked to the Wnt signaling pathway. This study expands on our previous work supporting the role of genetics in HRHS. We identified CNVs affecting crucial genes and signaling pathways involved in right heart development. ERBB4 and duplication of the 16q11-12 region are important areas for future investigation.
Details
- Title: Subtitle
- Copy number variants in hypoplastic right heart syndrome
- Creators
- Andreas Giannakou - Division of Intramural Population Health Research, Department of Health and Human Services, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MarylandRobert J Sicko - Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, New YorkDenise M Kay - Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, New YorkWei Zhang - Division of Intramural Population Health Research, Department of Health and Human Services, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MarylandPaul A Romitti - Department of Epidemiology, College of Public Health, The University of Iowa, Iowa City, IowaMichele Caggana - Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, New YorkGary M Shaw - Department of Pediatrics, Stanford University School of Medicine, Stanford, CaliforniaLaura L Jelliffe-Pawlowski - University of California San Francisco School of Medicine, San Francisco, CaliforniaJames L Mills - Division of Intramural Population Health Research, Department of Health and Human Services, 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.176(12), pp.2760-2767
- Publisher
- United States
- DOI
- 10.1002/ajmg.a.40527
- PMID
- 30289599
- ISSN
- 1552-4825
- eISSN
- 1552-4833
- Grant note
- HHSN275201100001I / NICHD NIH HHS U01DD001035 / ACL HHS HHSN27500005 / Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development U01DD001033 / ACL HHS U01 DD001035 / NCBDD CDC HHS U01 DD001223 / NCBDD CDC HHS
- Language
- English
- Date published
- 12/2018
- Academic Unit
- Epidemiology; Biostatistics
- Record Identifier
- 9983995004002771
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