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A Pathogenic Missense Variant (c.1617G>A, p.Met539Ile) in UBA1 Causing Infantile X-Linked Spinal Muscular Atrophy (SMAX2)
Background: Infantile X-linked spinal muscular atrophy (SMAX2) is a rare type of spinal muscular atrophy associated with UBA1 variants. Methods: Clinical imaging and neurophysiological tests were performed on a Chinese patient with SMAX2. Further, focused panel sequencing of UBA1 was carried out on...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059435/ https://www.ncbi.nlm.nih.gov/pubmed/32181232 http://dx.doi.org/10.3389/fped.2020.00064 |
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author | Wang, Xin Hua Zhang, Lin Mei Yang, Xue Zhou, Shui Zhen |
author_facet | Wang, Xin Hua Zhang, Lin Mei Yang, Xue Zhou, Shui Zhen |
author_sort | Wang, Xin Hua |
collection | PubMed |
description | Background: Infantile X-linked spinal muscular atrophy (SMAX2) is a rare type of spinal muscular atrophy associated with UBA1 variants. Methods: Clinical imaging and neurophysiological tests were performed on a Chinese patient with SMAX2. Further, focused panel sequencing of UBA1 was carried out on samples of both the proband and his maternal relatives. Results: The proband, a 4-year-old boy with the SMAX2 phenotype, suffered from reduced exercise capacity since infancy. His other symptoms included speech difficulties, severe nasal tone, reduced distal muscle strength, areflexia, and inadequate sucking ability. The brain MRI of the proband's showed normal results but the electromyography results showed multiple peripheral neurogenic lesions. Five male members of the proband's family were affected with the SMAX2 phenotype. They presented similar symptoms and had experienced a long and autonomous life. Molecular analysis revealed a novel missense variant (c.1617G>A, p.Met539Ile) in the exon 15 of UBA1. The proband's mother, as well as grandmother, carried the heterozygous missense UBA1 variant; whereas, the male patients from the family carried the hemizygotic variant. Conclusions: The affected members in this Chinese family showed unique features such as extended life span, no fractures, and cramps as compared with previously reported SMAX2 cases. The novel missense variant (c.1617G>A (p.Met539Ile) in UBA1 highlights the critical role of this gene in causing SMAX2 phenotype. |
format | Online Article Text |
id | pubmed-7059435 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-70594352020-03-16 A Pathogenic Missense Variant (c.1617G>A, p.Met539Ile) in UBA1 Causing Infantile X-Linked Spinal Muscular Atrophy (SMAX2) Wang, Xin Hua Zhang, Lin Mei Yang, Xue Zhou, Shui Zhen Front Pediatr Pediatrics Background: Infantile X-linked spinal muscular atrophy (SMAX2) is a rare type of spinal muscular atrophy associated with UBA1 variants. Methods: Clinical imaging and neurophysiological tests were performed on a Chinese patient with SMAX2. Further, focused panel sequencing of UBA1 was carried out on samples of both the proband and his maternal relatives. Results: The proband, a 4-year-old boy with the SMAX2 phenotype, suffered from reduced exercise capacity since infancy. His other symptoms included speech difficulties, severe nasal tone, reduced distal muscle strength, areflexia, and inadequate sucking ability. The brain MRI of the proband's showed normal results but the electromyography results showed multiple peripheral neurogenic lesions. Five male members of the proband's family were affected with the SMAX2 phenotype. They presented similar symptoms and had experienced a long and autonomous life. Molecular analysis revealed a novel missense variant (c.1617G>A, p.Met539Ile) in the exon 15 of UBA1. The proband's mother, as well as grandmother, carried the heterozygous missense UBA1 variant; whereas, the male patients from the family carried the hemizygotic variant. Conclusions: The affected members in this Chinese family showed unique features such as extended life span, no fractures, and cramps as compared with previously reported SMAX2 cases. The novel missense variant (c.1617G>A (p.Met539Ile) in UBA1 highlights the critical role of this gene in causing SMAX2 phenotype. Frontiers Media S.A. 2020-02-28 /pmc/articles/PMC7059435/ /pubmed/32181232 http://dx.doi.org/10.3389/fped.2020.00064 Text en Copyright © 2020 Wang, Zhang, Yang and Zhou. 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 | Pediatrics Wang, Xin Hua Zhang, Lin Mei Yang, Xue Zhou, Shui Zhen A Pathogenic Missense Variant (c.1617G>A, p.Met539Ile) in UBA1 Causing Infantile X-Linked Spinal Muscular Atrophy (SMAX2) |
title | A Pathogenic Missense Variant (c.1617G>A, p.Met539Ile) in UBA1 Causing Infantile X-Linked Spinal Muscular Atrophy (SMAX2) |
title_full | A Pathogenic Missense Variant (c.1617G>A, p.Met539Ile) in UBA1 Causing Infantile X-Linked Spinal Muscular Atrophy (SMAX2) |
title_fullStr | A Pathogenic Missense Variant (c.1617G>A, p.Met539Ile) in UBA1 Causing Infantile X-Linked Spinal Muscular Atrophy (SMAX2) |
title_full_unstemmed | A Pathogenic Missense Variant (c.1617G>A, p.Met539Ile) in UBA1 Causing Infantile X-Linked Spinal Muscular Atrophy (SMAX2) |
title_short | A Pathogenic Missense Variant (c.1617G>A, p.Met539Ile) in UBA1 Causing Infantile X-Linked Spinal Muscular Atrophy (SMAX2) |
title_sort | pathogenic missense variant (c.1617g>a, p.met539ile) in uba1 causing infantile x-linked spinal muscular atrophy (smax2) |
topic | Pediatrics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059435/ https://www.ncbi.nlm.nih.gov/pubmed/32181232 http://dx.doi.org/10.3389/fped.2020.00064 |
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