MCTP2 is a dosage-sensitive gene required for cardiac outflow tract development

Seema R. Lalani, Stephanie M. Ware, Xueqing Wang, Gladys Zapata, Qi Tian, Luis M. Franco, Zhengxin Jiang, Kristine Bucasas, Daryl A. Scott, Philippe M. Campeau, Neil Hanchard, Luis Umaña, Ashley Cast, Ankita Patel, Sau W. Cheung, Kim L. McBride, Molly Bray, A. Craig Chinault, Barbara A. Boggs, Miao HuangMariah R. Baker, Susan Hamilton, Jeff Towbin, John L. Jefferies, Susan D. Fernbach, Lorraine Potocki, John W. Belmont

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


Coarctation of the aorta (CoA) and hypoplastic left heart syndrome (HLHS) have been reported in rare individuals with large terminal deletions of chromosome15q26.However, nosingle gene important for left ventricularoutflow tract (LVOT) development has been identified in this region. Using array-comparative genomic hybridization, we identified two half-siblings with CoA with a 2.2 Mb deletion on 15q26.2, inherited from their mother, who was mosaic for this deletion. This interval contains an evolutionary conserved, protein-coding gene, MCTP2 (multiple C2-domains with two transmembrane regions 2). Using gene-specific array screening in 146 individualswith nonsyndromic LVOT obstructive defects, another individual with HLHS and CoA was found to have a de novo 41 kb intragenic duplication within MCTP2, predicted to result in premature truncation, p. F697X. Alteration of Mctp2 gene expression in Xenopus laevis embryos by morpholino knockdown and mRNA overexpression resulted in the failure of proper OT development, confirming the functional importance of this dosage-sensitive gene for cardiogenesis. Our results identify MCTP2 as a novel genetic cause of CoA and related cardiac malformations.

Original languageEnglish (US)
Article numberddt283
Pages (from-to)4339-4348
Number of pages10
JournalHuman molecular genetics
Issue number21
StatePublished - Nov 2013

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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