Clinical, neuropathological, and biochemical characterization of ALS in a large CHCHD10 R15L family.

ABSTRACT: Familial forms of ALS are potential candidates for gene-directed therapies, but many recently identified genes remain poorly characterized. Here, we provide a comprehensive clinical, neuropathological, and biochemical description of fALS caused by the heterozygous p.R15L missense mutation in the gene CHCHD10. Using a cross-sectional study design, we evaluate five affected and nine unaffected individuals from a large seven-generation pedigree with at least 68 affected members. The pedigree suggests a high (68 - 81%) but incomplete disease penetrance. Through cloning of the disease-allele from distant members of the family, we establish the disease haplotype in the family. Notably, the haplotype was distinct from that of a previously reported p.R15L mutation carrier with ALS, demonstrating t

SUBMITTER: Kwan JY 

PROVIDER: S-EPMC12486031 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature