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Hum Mol Genet 2013 Nov 01;2221:4339-48. doi: 10.1093/hmg/ddt283.
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MCTP2 is a dosage-sensitive gene required for cardiac outflow tract development.

Lalani SR , Ware SM , Wang X , Zapata G , Tian Q , Franco LM , Jiang Z , Bucasas K , Scott DA , Campeau PM , Hanchard N , Umaña L , Cast A , Patel A , Cheung SW , McBride KL , Bray M , Craig Chinault A , Boggs BA , Huang M , Baker MR , Hamilton S , Towbin J , Jefferies JL , Fernbach SD , Potocki L , Belmont JW .

Coarctation of the aorta (CoA) and hypoplastic left heart syndrome (HLHS) have been reported in rare individuals with large terminal deletions of chromosome 15q26. However, no single gene important for left ventricular outflow 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 individuals with non-syndromic 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.

PubMed ID: 23773997
PMC ID: PMC3792692
Article link: Hum Mol Genet
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: mctp2 nr2f5
GO keywords: outflow tract morphogenesis [+]
Morpholinos: mctp2 MO1 mctp2 MO2

Disease Ontology terms: chromosome 15q26-qter deletion syndrome [+]
References [+] :
Aranguren, Transcription factor COUP-TFII is indispensable for venous and lymphatic development in zebrafish and Xenopus laevis. 2011, Pubmed, Xenbase