Genetic and Clinical Studies of Peripheral Neuropathies with Three Small Heat Shock Protein Gene Variants in Korea

Small heat shock proteins (sHSPs) are ATP-independent chaperones that help correct the folding of denatured proteins and protect cells from stress. Mutations in , , and are implicated in inherited peripheral neuropathies (IPNs), such as Charcot-Marie-Tooth disease type 2 (CMT2) and distal hereditary motor neuropathies (dHMN). This study, using whole exome sequencing or targeted gene sequencing, identified 9 pathogenic or likely pathogenic variants in these three sHSP genes from 11 Korean IPN families. Most variants were located in the evolutionally well conserved α-crystallin domain, except for p.P182S and p.S187L in . As an atypical case, a patient with dHMN2 showed two compound heterozygous variants of p.R127Q and p.Y142H in , suggesting a putative case of recessive inheritance, which requires additional research to confirm. Three variants were located in the p.K141 residue, which seemed to be a mutational hot spot. There were no significant differences between patient groups, which divided by sHSP genes for clinical symptoms such as onset age, severity, and nerve conduction. Early-onset patients showed a tendency of slightly decreased sensory nerve conduction values compared with late-onset patients. As a first Korean IPN cohort study examining sHSP genes, these results will, we believe, be helpful for molecular diagnosis and care of patients with CMT2 and dHMN.