rs116840778

This retrospective multicenter cohort study of 23 patients with CAV3 mutations from 16 families describes the clinical, histological, and muscle imaging features of caveolinopathy with a mean follow-up of 24.2 years. The most common phenotype was exercise intolerance (52%), with 80% presenting calf hypertrophy and 65% showing rippling. The study identified four previously unreported CAV3 mutations (c.172T>C, c.194T>C, c.241G>C, and c.427_431del) alongside five previously reported variants, showing that caveolinopathy is a benign myopathy with limited functional impact despite diverse clinical presentations.

This study screened 663 patients with various muscle phenotypes and identified eight caveolinopathy cases from seven families with four CAV3 mutations: c.136G>A (p.A46T), c.99C>G (p.N33K), c.183C>A (p.S61R), and c.80G>A (p.R27Q). Two mutations (p.N33K and p.S61R) were novel. Caveolin-3 protein deficiency was a highly sensitive and specific marker of primary caveolinopathy, estimated at approximately 1% of both unclassified LGMD and other muscle phenotypes, demonstrating variable genotype-phenotype correlations even within families carrying identical mutations.

This multicenter retrospective cohort study of 23 patients with CAV3 gene mutations causing caveolinopathy identified eight heterozygous pathogenic variants and one biallelic deletion. Exercise intolerance was the most common phenotype (52%), with 80% of patients showing calf hypertrophy and 67% presenting with rippling phenomenon. Four novel CAV3 variants were identified: c.172T>C (p.Trp58Arg), c.194T>C (p.Phe65Ser), c.241G>C (p.Gly81Arg), and c.427_431del frameshift deletion.