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GENATLAS PHENOTYPE
last update : 13-07-2018
Symbol CMH4
Location 11p11.2
Name cardiomyopathy, familial, hypertrophic 4
Other name(s)
  • Left ventricular noncompaction 10
  • Cardiomyopathy, dilated, 1MM
  • Corresponding gene MYBPC3
    Other symbol(s) CMFH4, FHC4, LVNC10, CMD1MM
    Main clinical features
  • obstructive and dilated, an onset often delayed until middle age or old age, variable penetrance, particularly hypertrophic septum,
  • evolving into dilated cardiomyopathy
  • Genetic determination autosomal dominant
    Function/system disorder cardiovascular
    neuromuscular
    Type disease
    Gene product
    Name cardiac myosin binding protein-C3 (MYBPC3)
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
    insertion   truncated protein a G insertion in exon 25
    frameshift   haploinsufficiency splice site mutations in exon 6 and intron 31, a deletion in exon 13, and a nonsense mutation in exon 25 leading to premature termination codons, most likely causing loss of function and haploinsufficiency
    Remark(s)
  • genetic causes account for about half of presumed sporadic cases and nearly two thirds of familial cases of childhood-onset hypertrophy
  • R502W mutation does alter the predicted electrostatic properties of the C3 domain, and likely this mutation, and other HCM-linked mutations found within the same domain, may directly disrupt the interaction of MYBPC3 with other sarcomeric proteins (PMID: 25058872))
  • Genotype/Phenotype correlations
  • severe neonatal lethal hypertrophic cardiomyopathy caused by compound heterozygous for truncating mutations, and homozygous splice site mutation
  • p.F305Pfs*27 mutation carriers have a high probability to develop the disease between ages 30 years and 40 years with a significant major risk if they are men (PMID: 25740977))