Paediatric or syndromic cardiomyopathy

Gene: MYLK3

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 3 Mar 2022, 1:12 p.m. | Last Modified: 3 Mar 2022, 1:12 p.m.

Panel Version: 1.65

Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype on OMIM or Gene2Phenotype.

PMID: 29235529 describes 2 families with heterozygous variant in this gene. Family A - 2 sibs diagnosed with DCM at 9 and 10 months of age and affected mother diagnosed with DCM at 40 yo. As the children had a more severe phenotype and earlier onset than the mother the authors did further analysis and found the sibs had an additional variant in FLNC, which is also linked to DCM. The authors suggest this additional variant could account for the more severe phenotype in the children.

Family B - 2 brothers diagnosed with DCM at 56 and 52 yo, both have a heterozygous frameshift variant in this gene. Mother and sister had died young and DCM diagnosis is inconclusive.

PMID: 30690923 describes another case. Proband has a heterozygous frameshift variant in this gene. Rest of the family have no cardiac phenotype and no variants in this gene except for one daughter. Daughter has the same variant and has dilation of LV and ST-T abnormalities but these do not meet the criteria for DCM.

PMID: 32870709 describes three consanguineous families with homozygous variants in this gene.

There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.

Created: 20 Apr 2021, 10:18 a.m. | Last Modified: 20 Apr 2021, 10:18 a.m.

Panel Version: 1.35

I don't know

Two families reported with mono-allelic variants (one extension, one frameshift), and three consanguineous families reported with bi-allelic variants (two hmz frameshift, one hmz missense). Supportive mouse models.
Sources: Literature

Created: 16 Apr 2021, 9:24 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Dilated cardiomyopathy

Publications

• 29235529
• 31244672
• 32213617
• 32870709