Left Ventricular Noncompaction 7

A number sign (#) is used with this entry because of evidence that left ventricular noncompaction-7 (LVNC7) is caused by heterozygous mutation in the MIB1 gene (608677) on chromosome 18q11.

For a general phenotypic description and a discussion of genetic heterogeneity of LVNC, see 604169.

Molecular Genetics

Luxan et al. (2013) analyzed the MIB1 gene in 100 Spanish probands of southern European ancestry with left ventricular noncompaction and in 2 probands identified heterozygosity for a missense (V943F; 608677.0001) and a nonsense (R530X; 608677.0002) mutation, respectively. Each mutation segregated fully with disease in the respective family and neither was found in 263 Spanish controls or in the 1000 Genomes database. However, the V943F mutation was present in 3 of 5,375 individuals in the National Heart, Lung, and Blood Institute Grand Opportunity Exome Sequencing Project database, suggesting that MIB1 mutations may be frequent in populations with heart, lung, or blood diseases. Analysis of 12 additional candidate genes implicated in LVNC revealed no other mutations in either proband.

Animal Model

Luxan et al. (2013) generated mice with a conditional Mib1 loss-of-function allele and observed at embryonic day 16.5 that the mutant mice had a dilated heart with a thin compact myocardium and large noncompacted trabeculae protruding toward the ventricular lumen; similarly, newborn mice had large trabeculae in the left and right ventricles and a thin compact myocardium, and these features persisted into adulthood. Echocardiography in adult mice revealed prominent trabeculations and deep intertrabecular recesses in the mutants, with a noncompacted to compacted myocardium ratio of 2.0; the LVNC phenotype was confirmed by high-resolution cardiac MRI.