Causative mutation of middle age-onset spinocerebellar ataxia identified

Takeaway

  • Middle age-onset spinocerebellar ataxia, autosomal recessive (SCAR) is caused by a homozygous mutation, p.Ala175Thr, located in HSD17B4 that encodes peroxisomal D-bifunctional protein (DBP).

Why this matters

  • This study demonstrated that DBP deficiency caused by a homozygous mutation in HSD17B4 is responsible for middle age-onset, slowly progressive SCAR manifesting as cerebellar ataxia, sensorineural hearing loss, and/or peripheral neuropathy.

  • The authors also showed that Combined Annotation-Dependent Depletion (CADD) scores may be used to estimate the severity of DBP deficiencies.