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Mutations in the PLEKHG5 gene is relevant with autosomal recessive intermediate Charcot-Marie-Tooth disease
BACKGROUND: Mutations in the Pleckstrin homology domain-containing, family G member 5 (PLEKHG5) gene has been reported in a family harboring an autosomal recessive lower motor neuron disease (LMND). However, the PLEKHG5 mutation has not been described to cause Charcot-Marie-Tooth disease (CMT). METH...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728151/ https://www.ncbi.nlm.nih.gov/pubmed/23844677 http://dx.doi.org/10.1186/1750-1172-8-104 |
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author | Kim, Hyeon Jin Hong, Young Bin Park, Jin-Mo Choi, Yu-Ri Kim, Ye Jin Yoon, Bo Ram Koo, Heasoo Yoo, Jeong Hyun Kim, Sang Beom Park, Minhwa Chung, Ki Wha Choi, Byung-Ok |
author_facet | Kim, Hyeon Jin Hong, Young Bin Park, Jin-Mo Choi, Yu-Ri Kim, Ye Jin Yoon, Bo Ram Koo, Heasoo Yoo, Jeong Hyun Kim, Sang Beom Park, Minhwa Chung, Ki Wha Choi, Byung-Ok |
author_sort | Kim, Hyeon Jin |
collection | PubMed |
description | BACKGROUND: Mutations in the Pleckstrin homology domain-containing, family G member 5 (PLEKHG5) gene has been reported in a family harboring an autosomal recessive lower motor neuron disease (LMND). However, the PLEKHG5 mutation has not been described to cause Charcot-Marie-Tooth disease (CMT). METHODS: To identify the causative mutation in an autosomal recessive intermediate CMT (RI-CMT) family with childhood onset, whole exome sequencing (WES), histopathology, and lower leg MRIs were performed. Expression and activity of each mutant protein were analyzed. RESULTS: We identified novel compound heterozygous (p.Thr663Met and p.Gly820Arg) mutations in the PLEKHG5 gene in the present family. The patient revealed clinical manifestations of sensory neuropathy. Fatty replacements in the distal lower leg muscles were more severe than in the thigh muscles. Although the symptoms and signs of this patient harboring slow nerve conduction velocities suggested the possibility of demyelinating neuropathy, a distal sural nerve biopsy was compatible with axonal neuropathy. Immunohistochemical analysis revealed that the patient has a low level of PLEKHG5 in the distal sural nerve and an in vitro assay suggested that the mutant proteins have a defect in activating the NF-κB signaling pathway. CONCLUSIONS: This study identifies compound heterozygous PLEKHG5 mutations as the cause of RI-CMT. We suggest that PLEKHG5 might play a role in the peripheral motor and sensory nervous system. This study expands the phenotypic spectrum of PLEKHG5 mutations. |
format | Online Article Text |
id | pubmed-3728151 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-37281512013-07-31 Mutations in the PLEKHG5 gene is relevant with autosomal recessive intermediate Charcot-Marie-Tooth disease Kim, Hyeon Jin Hong, Young Bin Park, Jin-Mo Choi, Yu-Ri Kim, Ye Jin Yoon, Bo Ram Koo, Heasoo Yoo, Jeong Hyun Kim, Sang Beom Park, Minhwa Chung, Ki Wha Choi, Byung-Ok Orphanet J Rare Dis Research BACKGROUND: Mutations in the Pleckstrin homology domain-containing, family G member 5 (PLEKHG5) gene has been reported in a family harboring an autosomal recessive lower motor neuron disease (LMND). However, the PLEKHG5 mutation has not been described to cause Charcot-Marie-Tooth disease (CMT). METHODS: To identify the causative mutation in an autosomal recessive intermediate CMT (RI-CMT) family with childhood onset, whole exome sequencing (WES), histopathology, and lower leg MRIs were performed. Expression and activity of each mutant protein were analyzed. RESULTS: We identified novel compound heterozygous (p.Thr663Met and p.Gly820Arg) mutations in the PLEKHG5 gene in the present family. The patient revealed clinical manifestations of sensory neuropathy. Fatty replacements in the distal lower leg muscles were more severe than in the thigh muscles. Although the symptoms and signs of this patient harboring slow nerve conduction velocities suggested the possibility of demyelinating neuropathy, a distal sural nerve biopsy was compatible with axonal neuropathy. Immunohistochemical analysis revealed that the patient has a low level of PLEKHG5 in the distal sural nerve and an in vitro assay suggested that the mutant proteins have a defect in activating the NF-κB signaling pathway. CONCLUSIONS: This study identifies compound heterozygous PLEKHG5 mutations as the cause of RI-CMT. We suggest that PLEKHG5 might play a role in the peripheral motor and sensory nervous system. This study expands the phenotypic spectrum of PLEKHG5 mutations. BioMed Central 2013-07-12 /pmc/articles/PMC3728151/ /pubmed/23844677 http://dx.doi.org/10.1186/1750-1172-8-104 Text en Copyright © 2013 Kim et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Kim, Hyeon Jin Hong, Young Bin Park, Jin-Mo Choi, Yu-Ri Kim, Ye Jin Yoon, Bo Ram Koo, Heasoo Yoo, Jeong Hyun Kim, Sang Beom Park, Minhwa Chung, Ki Wha Choi, Byung-Ok Mutations in the PLEKHG5 gene is relevant with autosomal recessive intermediate Charcot-Marie-Tooth disease |
title | Mutations in the PLEKHG5 gene is relevant with autosomal recessive intermediate Charcot-Marie-Tooth disease |
title_full | Mutations in the PLEKHG5 gene is relevant with autosomal recessive intermediate Charcot-Marie-Tooth disease |
title_fullStr | Mutations in the PLEKHG5 gene is relevant with autosomal recessive intermediate Charcot-Marie-Tooth disease |
title_full_unstemmed | Mutations in the PLEKHG5 gene is relevant with autosomal recessive intermediate Charcot-Marie-Tooth disease |
title_short | Mutations in the PLEKHG5 gene is relevant with autosomal recessive intermediate Charcot-Marie-Tooth disease |
title_sort | mutations in the plekhg5 gene is relevant with autosomal recessive intermediate charcot-marie-tooth disease |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728151/ https://www.ncbi.nlm.nih.gov/pubmed/23844677 http://dx.doi.org/10.1186/1750-1172-8-104 |
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