The abstract is read at the publisher; the summary is JClub's.
A CHCHD10 p.R15L family shows a highly stereotyped flail arm syndrome phenotype, with ~4-fold elevated CHCHD10 protein in CSF and cervical-biased CHCHD10 aggregation.
- Why it matters: Many ALS genes lack detailed clinical, neuropathological, and biochemical characterization, limiting gene-directed therapy design and biomarker development for specific familial variants.
- What they did: In a cross-sectional study of five affected and nine unaffected relatives from a seven-generation pedigree, the team mapped a disease haplotype and assessed penetrance (68%–81%), then compared cervical versus lumbar pathology and measured CSF proteomics in variant carriers.
- The result: CHCHD10 R15L was stably expressed with substantial function in cells and a knock-in mouse model, while CSF showed ~4-fold higher CHCHD10 and carrier differentiation by NfL and PRPH, supporting toxic gain-of-function and biomarker use.
The findingWhy it mattersWhat they didThe result
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