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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 HSPB1, HSPB8, and HSPB3 are implicated in inherited peripheral neuropathies (IPNs), such as Charcot-Marie-Tooth disease type 2 (CMT2) and d...

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Autores principales: Lim, Si On, Jung, Na Young, Lee, Ah Jin, Choi, Hee Ji, Kwon, Hye Mi, Son, Wonseok, Nam, Soo Hyun, Choi, Byung-Ok, Chung, Ki Wha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8949397/
https://www.ncbi.nlm.nih.gov/pubmed/35328016
http://dx.doi.org/10.3390/genes13030462
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author Lim, Si On
Jung, Na Young
Lee, Ah Jin
Choi, Hee Ji
Kwon, Hye Mi
Son, Wonseok
Nam, Soo Hyun
Choi, Byung-Ok
Chung, Ki Wha
author_facet Lim, Si On
Jung, Na Young
Lee, Ah Jin
Choi, Hee Ji
Kwon, Hye Mi
Son, Wonseok
Nam, Soo Hyun
Choi, Byung-Ok
Chung, Ki Wha
author_sort Lim, Si On
collection PubMed
description 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.
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spelling pubmed-89493972022-03-26 Genetic and Clinical Studies of Peripheral Neuropathies with Three Small Heat Shock Protein Gene Variants in Korea Lim, Si On Jung, Na Young Lee, Ah Jin Choi, Hee Ji Kwon, Hye Mi Son, Wonseok Nam, Soo Hyun Choi, Byung-Ok Chung, Ki Wha Genes (Basel) Article 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. MDPI 2022-03-05 /pmc/articles/PMC8949397/ /pubmed/35328016 http://dx.doi.org/10.3390/genes13030462 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lim, Si On
Jung, Na Young
Lee, Ah Jin
Choi, Hee Ji
Kwon, Hye Mi
Son, Wonseok
Nam, Soo Hyun
Choi, Byung-Ok
Chung, Ki Wha
Genetic and Clinical Studies of Peripheral Neuropathies with Three Small Heat Shock Protein Gene Variants in Korea
title Genetic and Clinical Studies of Peripheral Neuropathies with Three Small Heat Shock Protein Gene Variants in Korea
title_full Genetic and Clinical Studies of Peripheral Neuropathies with Three Small Heat Shock Protein Gene Variants in Korea
title_fullStr Genetic and Clinical Studies of Peripheral Neuropathies with Three Small Heat Shock Protein Gene Variants in Korea
title_full_unstemmed Genetic and Clinical Studies of Peripheral Neuropathies with Three Small Heat Shock Protein Gene Variants in Korea
title_short Genetic and Clinical Studies of Peripheral Neuropathies with Three Small Heat Shock Protein Gene Variants in Korea
title_sort genetic and clinical studies of peripheral neuropathies with three small heat shock protein gene variants in korea
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8949397/
https://www.ncbi.nlm.nih.gov/pubmed/35328016
http://dx.doi.org/10.3390/genes13030462
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