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Clinical and biochemical characterization of amyotrophic lateral sclerosis in a CHCHD10 R15L family - PubMed

7 hours ago
  • #ALS
  • #CHCHD10
  • #Flail Arm Syndrome
  • The study characterized fALS caused by the CHCHD10 p.R15L mutation in a large family.
  • Disease showed high but incomplete penetrance (68-81%) and a stereotypic Flail Arm Syndrome presentation.
  • Neuropathology revealed CHCHD10 aggregation and neuronal loss in cervical spinal cord, without TDP-43 pathology.
  • Timed finger tapping may serve as a clinical biomarker for this ALS variant.
  • CHCHD10 R15L retains function in models, suggesting toxic gain-of-function, not loss-of-function, as disease mechanism.
  • CSF proteomics identified elevated CHCHD10 (~4-fold) and neurofilaments (NfL and PRPH) in mutation carriers.