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

Genes

Ah Jin Lee¹  Si On Lim¹  Wonseok Son¹  Hee Ji Choi¹  Ki Wha Chung¹  Na Young Jung¹  Hye Mi Kwon²  Byung-Ok Choi²  Soo Hyun Nam³ 

[1] Department of Biological Sciences, Kongju National University, 56 Gongjudaehak-ro, Gongju 32588, Korea;Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea;Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul 06351, Korea;

关键词: Charcot-Marie-Tooth disease type 2;    distal hereditary motor neuropathies;    HSPB1;    HSPB8;    HSPB3;    Korean;   

DOI  :  10.3390/genes13030462

来源: DOAJ

【 摘 要 】

Small heat shock proteins (sHSPs) are ATP-independent chaperones that help correct the folding of denatured proteins and protect cells from stress. Mutations in HSPB1, HSPB8, and HSPB3 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 HSPB1. As an atypical case, a patient with dHMN2 showed two compound heterozygous variants of p.R127Q and p.Y142H in HSPB1, suggesting a putative case of recessive inheritance, which requires additional research to confirm. Three HSPB8 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.

【 授权许可】

Unknown