| Symbol
| CMD1MM
|
| Location
| 11p11.2
|
| Name
|
cardiomyopathy, dilated, 1MM |
| Other name(s)
|
Left ventricular noncompaction 10 |
| Corresponding gene
|
MYBPC3
|
| Other symbol(s)
| CMFH4, FHC4, LVNC10
|
| 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
|
| Name
| cardiac myosin binding protein-C3 (MYBPC3)
|
| Gene mutation | Chromosome rearrangement | Effect | Comments |
|
|---|
| 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))
MYBPC3 truncation mutations enhance actomyosin contractile mechanics in human hypertrophic cardiomyopathy (PMID: 30550750)) |
| 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)) |