Novel missense variants in CFL2 affect F-actin depolymerisation and expand the disease spectrum of CFL2-related myopathy.

ABSTRACT: Cofilin-2, encoded by CFL2, is an actin-binding protein essential for regulating actin filament dynamics in skeletal muscle. Biallelic variants in CFL2 are associated with an ultra-rare, early-onset myopathy typically presenting as nemaline myopathy. Only 10 patients have been described to date from five unrelated families. Here, we describe two new cases from two unrelated families. The first proband presented clinically with rigid spine syndrome and a biopsy keeping with nemaline myopathy. The second proband presented with a relatively mild congenital myopathy which became rapidly progressive in the fourth decade, the muscle biopsy showed cytoplasmic bodies, internal nuclei and ringbinden. Exome and genome sequencing revealed three novel biallelic missense variants in CFL2, a homozygous

SUBMITTER: Dofash LNH 

PROVIDER: S-EPMC12368771 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature