Left ventricular noncompaction 10 (LVNC10) is associated with one of the three mutations in MYBPC3 gene:
Gly490Arg (rs200625851); 2-BP Del, 2919CT; Pro873Leu (rs371401403) (PMID:21551322) or with compound heterozygosity in MYBPC3 p.Lys505del and p.Pro955fs (PMID:24602869).
Cardiomyopathy, dilated, 1MM (CMD1MM) is associated with one of the four mutations in MYBPC3: Cys1264Phe (rs397514751); Gly490Arg (rs200625851); Ala833Thr (rs199865688) (PMID:20215591) and Asn948Thr (rs121909376) (PMID:12379228).
Probst et al. (2011) described 2 families with left ventricular noncompaction (LVNC) due to mutations in the MYBPC3 gene (see MOLECULAR GENETICS). In the first family, the male proband presented at age 70 years with dyspnea; family screening ... Probst et al. (2011) described 2 families with left ventricular noncompaction (LVNC) due to mutations in the MYBPC3 gene (see MOLECULAR GENETICS). In the first family, the male proband presented at age 70 years with dyspnea; family screening revealed that his asymptomatic son was also affected. Both patients had noncompacted segments of the left midventricular inferior and lateral wall. In the second family, the female proband had nonsustained ventricular flutter and received an implantable cardioverter-defibrillator; she had noncompacted segments of the apex and midventricular wall.
In a cohort of 63 unrelated white patients of western European descent with left ventricular noncompaction (LVNC), Probst et al. (2011) analyzed 8 sarcomere genes and identified 5 probands with 4 different heterozygous mutations in the MYBPC3 gene ... In a cohort of 63 unrelated white patients of western European descent with left ventricular noncompaction (LVNC), Probst et al. (2011) analyzed 8 sarcomere genes and identified 5 probands with 4 different heterozygous mutations in the MYBPC3 gene (see, e.g., 600958.0026-600958.0028). - Dilated Cardiomyopathy 1MM In 46 young patients with dilated cardiomyopathy (CMD), Daehmlow et al. (2002) screened 4 sarcomeric protein genes and identified heterozygosity for a missense mutation in the MYBPC3 gene (N948T; 600958.0013) in 1 patient. Daehmlow et al. (2002) noted that they could not confirm the disease-causing nature of the variant because family members were not available for the calculation of a 2-point lod score and further investigation. Ehlermann et al. (2008) screened the MYBPC3 gene in 87 patients with hypertrophic cardiomyopathy (see CMH4, 115197) and 71 patients with CMD and identified heterozygous mutations in 16 (18.4%) of the CMH patients and in 2 (2.8%) of the CMD patients. However, in the first CMD family, 3 additional carriers of the MYBPC3 missense mutation had no certain pathologic findings, and the authors noted that in the index patient, hypertensive heart disease could not be ruled out as the cause of his CMD phenotype. In the second CMD family, the 2 oldest carriers of the splice site mutation displayed CMD, whereas 4 younger mutation carriers showed CMH; the authors stated that it was most likely that the 2 older patients suffered from end-stage CMH with progression to a CMD phenotype. Screening of 5 additional cardiomyopathy-associated genes (MYH7, 160760; TNNT2, 191045; TNNI3, 191044; ACTC1, 102540; and TPM1, 191010) revealed no further mutations. Hershberger et al. (2010) screened 5 cardiomyopathy-associated genes in 312 patients with CMD, who had previously been studied by Hershberger et al. (2008), and identified 12 MYBPC3 variants in 13 (4.2%) of the probands, of which 2 were considered to be 'likely' disease-causing mutations: A833T (600958.0024) and C1264F (600958.0025). The A833T change was identified in affected individuals from 3 families; haplotype analysis suggested a founder mutation. Another mutation, G490R (600958.0026), which had previously been reported in association with hypertrophic cardiomyopathy (van Driest et al., 2004; Morita et al., 2008), was detected in a CMD proband and designated as 'possibly' causative because family members were not available for segregation analysis.