Human molecular genetic and functional studies identify TRIM63, encoding Muscle RING Finger Protein 1, as a novel gene for human hypertrophic cardiomyopathy.

ABSTRACT:

Rationale

A delicate balance between protein synthesis and degradation maintains cardiac size and function. TRIM63 encoding Muscle RING Finger 1 (MuRF1) maintains muscle protein homeostasis by tagging the sarcomere proteins with ubiquitin for subsequent degradation by the ubiquitin-proteasome system (UPS).

Objective

To determine the pathogenic role of TRIM63 in human hypertrophic cardiomyopathy (HCM).

Methods and results

Sequencing of TRIM63 gene in 302 HCM probands (250 white individuals) and 339 control subjects (262 white individuals) led to identification of 2 missense (p.A48V and p.I130M) and a deletion (p.Q247*) variants exclusively in the HCM probands. These 3 variants were absent in 751 additional control subjects screened by TaqMan assays. Likewise, rare vari

SUBMITTER: Chen SN 

PROVIDER: S-EPMC3482312 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature