Copy-number variant analysis of classic heterotaxy highlights the importance of body patterning pathways

Details

• Alternative Title:
  Hum Genet
• Personal Author:
  Hagen, Erin M. ; Sicko, Robert J. ; Kay, Denise M. ; Rigler, Shannon L. ; Dimopoulos, Aggeliki ; Ahmad, Shabbir ; Doleman, Margaret H. ; Fan, Ruzong ; Romitti, Paul A. ; Browne, Marilyn L. ; Caggana, Michele ; Brody, Lawrence C. ; Shaw, Gary M. ; Jelliffe-Pawlowski, Laura L. ; Mills, James L.
• Description:
  Classic heterotaxy consists of congenital heart defects with abnormally positioned thoracic and abdominal organs. We aimed to uncover novel, genomic copy-number variants (CNVs) in classic heterotaxy cases. A microarray containing 2.5 million single-nucleotide polymorphisms (SNPs) was used to genotype 69 infants (cases) with classic heterotaxy identified from California live births from 1998 to 2009. CNVs were identified using the PennCNV software. We identified 56 rare CNVs encompassing genes in the NODAL (NIPBL, TBX6), BMP (PPP4C), and WNT (FZD3) signaling pathways, not previously linked to classic heterotaxy. We also identified a CNV involving FGF12, a gene previously noted in a classic heterotaxy case. CNVs involving RBFOX1 and near MIR302F were detected in multiple cases. Our findings illustrate the importance of body patterning pathways for cardiac development and left/right axes determination. FGF12, RBFOX1, and MIR302F could be important in human heterotaxy, because they were noted in multiple cases. Further investigation into genes involved in the NODAL, BMP, and WNT body patterning pathways and into the dosage effects of FGF12, RBFOX1, and MIR302F is warranted.
• Keywords:
  Body Patterning DNA Copy Number Variations Female Fibroblast Growth Factors Genotype Heart Defects, Congenital Heterotaxy Syndrome Humans Infant Male MicroRNAs Polymorphism, Single Nucleotide RNA Splicing Factors Signal Transduction

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• Source:
  Hum Genet. 135(12):1355-1364
• Pubmed ID:
  27637763
• Pubmed Central ID:
  PMC5065782
• Document Type:
  Journal Article
• Funding:
  U01 DD001033/DD/NCBDD CDC HHSUnited States/ ; U01DD001033/ACL/ACL HHSUnited States/ ; R01 HL092330/HL/NHLBI NIH HHSUnited States/ ; U01 DD001035/DD/NCBDD CDC HHSUnited States/ ; HHSN275201100001I/HD/NICHD NIH HHSUnited States/ ; HHSN275201100001C/HD/NICHD NIH HHSUnited States/ ; N01DK73431/HD/NICHD NIH HHSUnited States/ ; Z01 HD008792-01/ImNIH/Intramural NIH HHSUnited States/ ; HHSN275201100001G/HD/NICHD NIH HHSUnited States/
• Volume:
  135
• Issue:
  12
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:c946c53a5a9f7dd9e043b3790c12544cd7ce7906e4de22ab7df69a12ba831190
• Download URL:
  https://stacks.cdc.gov/view/cdc/42933/cdc_42933_DS1.pdf
• File Type:
  [PDF - 357.35 KB ]