Novel copy-number variants in a population-based investigation of classic heterotaxy

Details

• Alternative Title:
  Genet Med
• Personal Author:
  Rigler, Shannon L. ; Kay, Denise M. ; Sicko, Robert J. ; Fan, Ruzong ; Liu, Aiyi ; Caggana, Michele ; Browne, Marilyn L. ; Druschel, Charlotte M. ; Romitti, Paul A. ; Brody, Lawrence C. ; Mills, James L.
  More +
• Description:
  Purpose ; Heterotaxy is a clinically and genetically heterogeneous disorder. We investigated whether screening cases restricted to a classic phenotype would result in the discovery of novel, potentially causal copy-number variants. ; Methods ; We identified 77 cases of classic heterotaxy from all live births in New York State during 1998–2005. DNA extracted from each infant’s newborn dried blood spot was genotyped with a microarray containing 2.5 million single-nucleotide polymorphisms. Copy-number variants were identified with PennCNV and cnvPartition software. Candidates were selected for follow-up if they were absent in unaffected controls, contained 10 or more consecutive probes, and had minimal overlap with variants published in the Database of Genomic Variants. ; Results ; We identified 20 rare copy-number variants including a deletion of BMP2, which has been linked to laterality disorders in mice but not previously reported in humans. We also identified a large, terminal deletion of 10q and a microdeletion at 1q23.1 involving the MNDA gene; both are rare variants suspected to be associated with heterotaxy. ; Conclusion ; Our findings implicate rare copy-number variants in classic heterotaxy and highlight several candidate gene regions for further investigation. We also demonstrate the efficacy of copy-number variant genotyping in blood spots using microarrays.
• Subjects:
  • Case-Control Studies
  • Comparative Genomic Hybridization
  • Congenital Abnormalities
  • DNA Copy Number Variations
  • Female
  • Genetic Association Studies
  • Genotype
  • Humans
  • Infant
  • Infant, Newborn
  More +
• Keywords:
  • BMP2 gene
  • congenital heart disease
  • copy-number variant
  • heterotaxy
  • MNDA gene
• Source:
  Genet Med. 17(5):348-357
• Pubmed ID:
  25232849
• Pubmed Central ID:
  PMC5901701
• Document Type:
  Journal Article
• Funding:
  U01 DD001035/DD/NCBDD CDC HHSUnited States/ ; WT_/Wellcome TrustUnited Kingdom/ ; N01DK73431/HD/NICHD NIH HHSUnited States/ ; HHSN27500005/PHS HHSUnited States/ ; U01 DD000492/DD/NCBDD CDC HHSUnited States/ ; N01-DK-73431/DK/NIDDK NIH HHSUnited States/
• Volume:
  17
• Issue:
  5
• Download URL:
  https://stacks.cdc.gov/view/cdc/53502/cdc_53502_DS1.pdf
• File Type:
  [PDF - 898.52 KB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:d95c6486ea49c96b61cd7e7bec233fb42dc95406d3cfa483b241af602146fa6a