Cargando…
Spinal Muscular Atrophy with Progressive Myoclonic Epilepsy (SMA-PME): three new cases and review of the mutational spectrum
BACKGROUND: Spinal muscular atrophy (SMA) could be classified as 5q and non-5q, based on the chromosomal location of causative genes. A rare form of non-5q SMA is an autosomal-recessive condition called spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME), phenotypically characteriz...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10246360/ https://www.ncbi.nlm.nih.gov/pubmed/37280710 http://dx.doi.org/10.1186/s13052-023-01474-z |
_version_ | 1785055016639266816 |
---|---|
author | Najafi, Ali Tasharrofi, Behnoosh Zandsalimi, Farshid Rasulinezhad, Maryam Ghahvechi Akbari, Masood Zamani, Gholamreza Ashrafi, Mahmoud Reza Heidari, Morteza |
author_facet | Najafi, Ali Tasharrofi, Behnoosh Zandsalimi, Farshid Rasulinezhad, Maryam Ghahvechi Akbari, Masood Zamani, Gholamreza Ashrafi, Mahmoud Reza Heidari, Morteza |
author_sort | Najafi, Ali |
collection | PubMed |
description | BACKGROUND: Spinal muscular atrophy (SMA) could be classified as 5q and non-5q, based on the chromosomal location of causative genes. A rare form of non-5q SMA is an autosomal-recessive condition called spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME), phenotypically characterized by myoclonic and generalized seizures with progressive neurological deterioration. SMA-PME is a clinically heterogeneous disorder that arises from biallelic pathogenic variants in ASAH1 gene. METHODS: Following clinical and primary laboratory assessments, whole-exome sequencing was performed to detect the disease-causing variants in three cases of SMA-PME from different families. Also, Multiplex ligation-dependent probe amplification (MLPA) was employed for determining the copy numbers of SMN1 and SMN2 genes to rule out 5q SMA. RESULTS: Exome sequencing revealed two different homozygous missense mutations (c.109 C > A [p.Pro37Thr] or c.125 C > T [p.Thr42Met]) in exon 2 of the ASAH1 gene in the affected members of the families. Sanger sequencing of the other family members showed the expected heterozygous carriers. In addition, no clinically relevant variant was identified in patients by MLPA. CONCLUSION: This study describes two different ASAH1 mutations and the clinical picture of 3 SMA-PME patients. In addition, previously reported mutations have been reviewed. This study could help to fortify the database of this rare disease with more clinical and genomic data. |
format | Online Article Text |
id | pubmed-10246360 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-102463602023-06-08 Spinal Muscular Atrophy with Progressive Myoclonic Epilepsy (SMA-PME): three new cases and review of the mutational spectrum Najafi, Ali Tasharrofi, Behnoosh Zandsalimi, Farshid Rasulinezhad, Maryam Ghahvechi Akbari, Masood Zamani, Gholamreza Ashrafi, Mahmoud Reza Heidari, Morteza Ital J Pediatr Research BACKGROUND: Spinal muscular atrophy (SMA) could be classified as 5q and non-5q, based on the chromosomal location of causative genes. A rare form of non-5q SMA is an autosomal-recessive condition called spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME), phenotypically characterized by myoclonic and generalized seizures with progressive neurological deterioration. SMA-PME is a clinically heterogeneous disorder that arises from biallelic pathogenic variants in ASAH1 gene. METHODS: Following clinical and primary laboratory assessments, whole-exome sequencing was performed to detect the disease-causing variants in three cases of SMA-PME from different families. Also, Multiplex ligation-dependent probe amplification (MLPA) was employed for determining the copy numbers of SMN1 and SMN2 genes to rule out 5q SMA. RESULTS: Exome sequencing revealed two different homozygous missense mutations (c.109 C > A [p.Pro37Thr] or c.125 C > T [p.Thr42Met]) in exon 2 of the ASAH1 gene in the affected members of the families. Sanger sequencing of the other family members showed the expected heterozygous carriers. In addition, no clinically relevant variant was identified in patients by MLPA. CONCLUSION: This study describes two different ASAH1 mutations and the clinical picture of 3 SMA-PME patients. In addition, previously reported mutations have been reviewed. This study could help to fortify the database of this rare disease with more clinical and genomic data. BioMed Central 2023-06-06 /pmc/articles/PMC10246360/ /pubmed/37280710 http://dx.doi.org/10.1186/s13052-023-01474-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Najafi, Ali Tasharrofi, Behnoosh Zandsalimi, Farshid Rasulinezhad, Maryam Ghahvechi Akbari, Masood Zamani, Gholamreza Ashrafi, Mahmoud Reza Heidari, Morteza Spinal Muscular Atrophy with Progressive Myoclonic Epilepsy (SMA-PME): three new cases and review of the mutational spectrum |
title | Spinal Muscular Atrophy with Progressive Myoclonic Epilepsy (SMA-PME): three new cases and review of the mutational spectrum |
title_full | Spinal Muscular Atrophy with Progressive Myoclonic Epilepsy (SMA-PME): three new cases and review of the mutational spectrum |
title_fullStr | Spinal Muscular Atrophy with Progressive Myoclonic Epilepsy (SMA-PME): three new cases and review of the mutational spectrum |
title_full_unstemmed | Spinal Muscular Atrophy with Progressive Myoclonic Epilepsy (SMA-PME): three new cases and review of the mutational spectrum |
title_short | Spinal Muscular Atrophy with Progressive Myoclonic Epilepsy (SMA-PME): three new cases and review of the mutational spectrum |
title_sort | spinal muscular atrophy with progressive myoclonic epilepsy (sma-pme): three new cases and review of the mutational spectrum |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10246360/ https://www.ncbi.nlm.nih.gov/pubmed/37280710 http://dx.doi.org/10.1186/s13052-023-01474-z |
work_keys_str_mv | AT najafiali spinalmuscularatrophywithprogressivemyoclonicepilepsysmapmethreenewcasesandreviewofthemutationalspectrum AT tasharrofibehnoosh spinalmuscularatrophywithprogressivemyoclonicepilepsysmapmethreenewcasesandreviewofthemutationalspectrum AT zandsalimifarshid spinalmuscularatrophywithprogressivemyoclonicepilepsysmapmethreenewcasesandreviewofthemutationalspectrum AT rasulinezhadmaryam spinalmuscularatrophywithprogressivemyoclonicepilepsysmapmethreenewcasesandreviewofthemutationalspectrum AT ghahvechiakbarimasood spinalmuscularatrophywithprogressivemyoclonicepilepsysmapmethreenewcasesandreviewofthemutationalspectrum AT zamanigholamreza spinalmuscularatrophywithprogressivemyoclonicepilepsysmapmethreenewcasesandreviewofthemutationalspectrum AT ashrafimahmoudreza spinalmuscularatrophywithprogressivemyoclonicepilepsysmapmethreenewcasesandreviewofthemutationalspectrum AT heidarimorteza spinalmuscularatrophywithprogressivemyoclonicepilepsysmapmethreenewcasesandreviewofthemutationalspectrum |