SETX and Distal Hereditary Motor Neuropathy

Distal hereditary motor neuropathy (dHMN) is an autosomal dominant disorder characterized by progressive distal weakness due to spinal α-motor neuron involvement. In a cohort of 112 familial and isolated dHMN patients, targeted screening of seven known dHMN genes identified SETX pathogenic variants among cases, contributing to the nine distinct mutations found in HSPB8, HSPB1, BSCL2, and SETX in 17 patients ([PMID:18325928]). Inheritance is autosomal dominant with no detailed segregation data reported and without functional assays showing SETX variant pathogenicity in dHMN. The evidence for a SETX–dHMN association is limited to this single case series, lacking replication or mechanistic follow-up.

Overall, the clinical validity of SETX in distal hereditary motor neuropathy is limited. Further case accumulation, segregation studies, and functional modeling are required. Key take-home: SETX remains a candidate gene for autosomal dominant dHMN, but additional genetic and experimental data are needed before it can inform diagnostic testing or therapeutic strategies.

References

• Brain • 2008 • Relative contribution of mutations in genes for autosomal dominant distal hereditary motor neuropathies: a genotype-phenotype correlation study PMID:18325928

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