FIG4 mutattions

Patent Granted Mutations in the FIG4 gene cause the rare autosomal recessive Charcot-Marie-Tooth peripheral neuropathy type 4J (CMT4J).[16] FIG4 mutations are also found (without proven causation) in patients with amyotrophic lateral sclerosis (ALS).[19] Most CMT4J patients (15 out of the reported 16) are compound heterozygotes, i.e., the one FIG4 allele is null whereas the other encodes a mutant protein with threonine for isoleucine substitution at position 41.[20] The Sac3I41T point mutation abrogates the protective action of ArPIKfyve on Sac3 half-life yet the association between the two is largely preserved.[17] Consequently, the Sac3I41T protein level in patient fibroblasts is very low due to mutant degradation in the proteasome.