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Case report: A compound heterozygous mutations in ARSA associated with adult-onset metachromatic leukodystrophy
Metachromatic Leukodystrophy (MLD) is a rare autosomal recessive disease, which is caused by mutations in the arylsulfatase A (ARSA) gene. The ARSA gene is located on chromosome 22q13, containing eight exons. According to the age of onset, MLD can be divided into late infantile type, juvenile type,...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9619211/ https://www.ncbi.nlm.nih.gov/pubmed/36324388 http://dx.doi.org/10.3389/fneur.2022.1011019 |
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author | Wang, Bing-lei Lu, Fen-lei Sun, Yu-chen Wang, Hui-juan |
author_facet | Wang, Bing-lei Lu, Fen-lei Sun, Yu-chen Wang, Hui-juan |
author_sort | Wang, Bing-lei |
collection | PubMed |
description | Metachromatic Leukodystrophy (MLD) is a rare autosomal recessive disease, which is caused by mutations in the arylsulfatase A (ARSA) gene. The ARSA gene is located on chromosome 22q13, containing eight exons. According to the age of onset, MLD can be divided into late infantile type, juvenile type, and adult type. Adult MLD has an insidious onset after the age of 16 years. Additionally, intellectual as well as behavioral changes, such as memory deficits or emotional instability, are commonly the first presenting symptoms. There is a study that reported an adult-onset MLD manifested cognitive impairment progressively due to compound heterozygous mutations of NM_000487: c.[185_186dupCA], p.(Asp63GlnfsTer18), and NM_000487: c.[154G>T], p.(Gly172Cys), rs74315271 in the ARSA gene, finding that the c.[154G>T], p.(Gly172Cys) is a novel missense mutation. Brain magnetic resonance imaging (MRI) revealed symmetrical demyelination of white matter. The activity of ARSA enzymatic in leukocytes decreased. Nerve conduction studies displayed that evidence of polyneuropathy was superimposed upon diffuse, uniform demyelinating, and sensorimotor polyneuropathy. Family genes revealed that each family member carried one of two heterozygous mutant genes. She has been discharged and is currently being followed up. This study found a compound heterozygous mutation in the ARSA gene associated with MLD and identified a novel missense mutation NM_000487: c.[154G>T], p.(Gly172Cys), rs74315271. This will provide a critical clue for prenatal diagnosis of the offspring in this family, and expand the mutation spectrum of MLD-related ARSA. |
format | Online Article Text |
id | pubmed-9619211 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-96192112022-11-01 Case report: A compound heterozygous mutations in ARSA associated with adult-onset metachromatic leukodystrophy Wang, Bing-lei Lu, Fen-lei Sun, Yu-chen Wang, Hui-juan Front Neurol Neurology Metachromatic Leukodystrophy (MLD) is a rare autosomal recessive disease, which is caused by mutations in the arylsulfatase A (ARSA) gene. The ARSA gene is located on chromosome 22q13, containing eight exons. According to the age of onset, MLD can be divided into late infantile type, juvenile type, and adult type. Adult MLD has an insidious onset after the age of 16 years. Additionally, intellectual as well as behavioral changes, such as memory deficits or emotional instability, are commonly the first presenting symptoms. There is a study that reported an adult-onset MLD manifested cognitive impairment progressively due to compound heterozygous mutations of NM_000487: c.[185_186dupCA], p.(Asp63GlnfsTer18), and NM_000487: c.[154G>T], p.(Gly172Cys), rs74315271 in the ARSA gene, finding that the c.[154G>T], p.(Gly172Cys) is a novel missense mutation. Brain magnetic resonance imaging (MRI) revealed symmetrical demyelination of white matter. The activity of ARSA enzymatic in leukocytes decreased. Nerve conduction studies displayed that evidence of polyneuropathy was superimposed upon diffuse, uniform demyelinating, and sensorimotor polyneuropathy. Family genes revealed that each family member carried one of two heterozygous mutant genes. She has been discharged and is currently being followed up. This study found a compound heterozygous mutation in the ARSA gene associated with MLD and identified a novel missense mutation NM_000487: c.[154G>T], p.(Gly172Cys), rs74315271. This will provide a critical clue for prenatal diagnosis of the offspring in this family, and expand the mutation spectrum of MLD-related ARSA. Frontiers Media S.A. 2022-10-17 /pmc/articles/PMC9619211/ /pubmed/36324388 http://dx.doi.org/10.3389/fneur.2022.1011019 Text en Copyright © 2022 Wang, Lu, Sun and Wang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neurology Wang, Bing-lei Lu, Fen-lei Sun, Yu-chen Wang, Hui-juan Case report: A compound heterozygous mutations in ARSA associated with adult-onset metachromatic leukodystrophy |
title | Case report: A compound heterozygous mutations in ARSA associated with adult-onset metachromatic leukodystrophy |
title_full | Case report: A compound heterozygous mutations in ARSA associated with adult-onset metachromatic leukodystrophy |
title_fullStr | Case report: A compound heterozygous mutations in ARSA associated with adult-onset metachromatic leukodystrophy |
title_full_unstemmed | Case report: A compound heterozygous mutations in ARSA associated with adult-onset metachromatic leukodystrophy |
title_short | Case report: A compound heterozygous mutations in ARSA associated with adult-onset metachromatic leukodystrophy |
title_sort | case report: a compound heterozygous mutations in arsa associated with adult-onset metachromatic leukodystrophy |
topic | Neurology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9619211/ https://www.ncbi.nlm.nih.gov/pubmed/36324388 http://dx.doi.org/10.3389/fneur.2022.1011019 |
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