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Peripheral Myelin Protein 22 Gene Mutations in Charcot-Marie-Tooth Disease Type 1E Patients

Duplication and deletion of the peripheral myelin protein 22 (PMP22) gene cause Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP), respectively, while point mutations or small insertions and deletions (indels) usually cause CMT type 1E (C...

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Autores principales: Jung, Na Young, Kwon, Hye Mi, Nam, Da Eun, Tamanna, Nasrin, Lee, Ah Jin, Kim, Sang Beom, Choi, Byung-Ok, Chung, Ki Wha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9321036/
https://www.ncbi.nlm.nih.gov/pubmed/35886002
http://dx.doi.org/10.3390/genes13071219
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author Jung, Na Young
Kwon, Hye Mi
Nam, Da Eun
Tamanna, Nasrin
Lee, Ah Jin
Kim, Sang Beom
Choi, Byung-Ok
Chung, Ki Wha
author_facet Jung, Na Young
Kwon, Hye Mi
Nam, Da Eun
Tamanna, Nasrin
Lee, Ah Jin
Kim, Sang Beom
Choi, Byung-Ok
Chung, Ki Wha
author_sort Jung, Na Young
collection PubMed
description Duplication and deletion of the peripheral myelin protein 22 (PMP22) gene cause Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP), respectively, while point mutations or small insertions and deletions (indels) usually cause CMT type 1E (CMT1E) or HNPP. This study was performed to identify PMP22 mutations and to analyze the genotype–phenotype correlation in Korean CMT families. By the application of whole-exome sequencing (WES) and targeted gene panel sequencing (TS), we identified 14 pathogenic or likely pathogenic PMP22 mutations in 21 families out of 850 CMT families who were negative for 17p12 (PMP22) duplication. Most mutations were located in the well-conserved transmembrane domains. Of these, eight mutations were not reported in other populations. High frequencies of de novo mutations were observed, and the mutation sites of c.68C>G and c.215C>T were suggested as the mutational hotspots. Affected individuals showed an early onset-severe phenotype and late onset-mild phenotype, and more than 40% of the CMT1E patients showed hearing loss. Physical and electrophysiological symptoms of the CMT1E patients were more severely damaged than those of CMT1A while similar to CMT1B caused by MPZ mutations. Our results will be useful for the reference data of Korean CMT1E and the molecular diagnosis of CMT1 with or without hearing loss.
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spelling pubmed-93210362022-07-27 Peripheral Myelin Protein 22 Gene Mutations in Charcot-Marie-Tooth Disease Type 1E Patients Jung, Na Young Kwon, Hye Mi Nam, Da Eun Tamanna, Nasrin Lee, Ah Jin Kim, Sang Beom Choi, Byung-Ok Chung, Ki Wha Genes (Basel) Article Duplication and deletion of the peripheral myelin protein 22 (PMP22) gene cause Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP), respectively, while point mutations or small insertions and deletions (indels) usually cause CMT type 1E (CMT1E) or HNPP. This study was performed to identify PMP22 mutations and to analyze the genotype–phenotype correlation in Korean CMT families. By the application of whole-exome sequencing (WES) and targeted gene panel sequencing (TS), we identified 14 pathogenic or likely pathogenic PMP22 mutations in 21 families out of 850 CMT families who were negative for 17p12 (PMP22) duplication. Most mutations were located in the well-conserved transmembrane domains. Of these, eight mutations were not reported in other populations. High frequencies of de novo mutations were observed, and the mutation sites of c.68C>G and c.215C>T were suggested as the mutational hotspots. Affected individuals showed an early onset-severe phenotype and late onset-mild phenotype, and more than 40% of the CMT1E patients showed hearing loss. Physical and electrophysiological symptoms of the CMT1E patients were more severely damaged than those of CMT1A while similar to CMT1B caused by MPZ mutations. Our results will be useful for the reference data of Korean CMT1E and the molecular diagnosis of CMT1 with or without hearing loss. MDPI 2022-07-08 /pmc/articles/PMC9321036/ /pubmed/35886002 http://dx.doi.org/10.3390/genes13071219 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
Jung, Na Young
Kwon, Hye Mi
Nam, Da Eun
Tamanna, Nasrin
Lee, Ah Jin
Kim, Sang Beom
Choi, Byung-Ok
Chung, Ki Wha
Peripheral Myelin Protein 22 Gene Mutations in Charcot-Marie-Tooth Disease Type 1E Patients
title Peripheral Myelin Protein 22 Gene Mutations in Charcot-Marie-Tooth Disease Type 1E Patients
title_full Peripheral Myelin Protein 22 Gene Mutations in Charcot-Marie-Tooth Disease Type 1E Patients
title_fullStr Peripheral Myelin Protein 22 Gene Mutations in Charcot-Marie-Tooth Disease Type 1E Patients
title_full_unstemmed Peripheral Myelin Protein 22 Gene Mutations in Charcot-Marie-Tooth Disease Type 1E Patients
title_short Peripheral Myelin Protein 22 Gene Mutations in Charcot-Marie-Tooth Disease Type 1E Patients
title_sort peripheral myelin protein 22 gene mutations in charcot-marie-tooth disease type 1e patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9321036/
https://www.ncbi.nlm.nih.gov/pubmed/35886002
http://dx.doi.org/10.3390/genes13071219
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