Investigating genotype-phenotype correlation of limb-girdle muscular dystrophy R8: association of clinical severity, protein biological function and protein oligomerization.

ABSTRACT: Limb-girdle muscular dystrophy R8 (LGMD R8) is a hereditary muscle disease caused by biallelic defects in E3 ubiquitinated ligase gene (TRIM32). LGMD R8 is featured by high genetic heterogeneity and phenotypic diversity, most pathogenic variants are missense variants located in the NHL domain, but the genotype-phenotype correlation remains unclear. We hypothesized that various missense variants in NHL domain might have different degrees of impact on the structure and function of the protein, thus resulting in disease variability. Firstly, by analyzing present patients' clinical data, we screen out 4 variants: R394H, D487N, V591M and P619S. Patients homozygous for the aforementioned variants exhibited significant phenotypic variability, including variations in age of onset and age of any wa

SUBMITTER: Liang X 

PROVIDER: S-EPMC11877741 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature