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Expression assay of the COLQ in a family with congenital myasthenic syndrome and symptomatic carriers
Congenital myasthenic syndromes‐5 (CMS5) is a rare autosomal recessive heterogeneous disorder, caused by pathogenic variants in the COLQ that lead to skeletal muscle weakness and abnormal fatigability. The onset is usually from birth to childhood. Disease‐causing variants in the collagen‐like tail s...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10593973/ https://www.ncbi.nlm.nih.gov/pubmed/37881193 http://dx.doi.org/10.1002/ccr3.8062 |
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author | Mohammadi, Mohammad Farid Fateh, Sahand Tehrani Aghajani, Hadi Bahramy, Afshin Zaheryani, Seyed Mohammad Salar Behroozi, Javad Kahani, Seyyed Mohammad Mohammadi, Pouria Garshasbi, Masoud |
author_facet | Mohammadi, Mohammad Farid Fateh, Sahand Tehrani Aghajani, Hadi Bahramy, Afshin Zaheryani, Seyed Mohammad Salar Behroozi, Javad Kahani, Seyyed Mohammad Mohammadi, Pouria Garshasbi, Masoud |
author_sort | Mohammadi, Mohammad Farid |
collection | PubMed |
description | Congenital myasthenic syndromes‐5 (CMS5) is a rare autosomal recessive heterogeneous disorder, caused by pathogenic variants in the COLQ that lead to skeletal muscle weakness and abnormal fatigability. The onset is usually from birth to childhood. Disease‐causing variants in the collagen‐like tail subunit are the most explained etiology in synaptic CMS, causing defected acetylcholinesterase. In this study whole‐exome sequencing (WES) was performed in an affected boy with muscle weakness, ophthalmoplegia, and bilateral ptosis and gene expression assay by qRT‐PCR was performed in entire family. A homozygous nonsense variant in the COLQ [NM_005677.4:c.679C>T], (p.Arg227Ter) was identified in the proband. Segregation analysis by Sanger sequencing confirmed the homozygous state in the proband and heterozygous state in his parents and four of the siblings. The mRNA expression level in the proband was 0.02 of a healthy person, and in the carriers were 0.42 of a healthy person. This study presents an Iranian family with two affected children and eight symptomatic carriers with attenuated mRNA expression. This study provides evidence that carriers of the COLQ disease‐causing variants could become symptomatic with some yet unknown pathogenesis mechanism and underscore the importance of further investigations to elucidate this mechanism. |
format | Online Article Text |
id | pubmed-10593973 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-105939732023-10-25 Expression assay of the COLQ in a family with congenital myasthenic syndrome and symptomatic carriers Mohammadi, Mohammad Farid Fateh, Sahand Tehrani Aghajani, Hadi Bahramy, Afshin Zaheryani, Seyed Mohammad Salar Behroozi, Javad Kahani, Seyyed Mohammad Mohammadi, Pouria Garshasbi, Masoud Clin Case Rep Case Report Congenital myasthenic syndromes‐5 (CMS5) is a rare autosomal recessive heterogeneous disorder, caused by pathogenic variants in the COLQ that lead to skeletal muscle weakness and abnormal fatigability. The onset is usually from birth to childhood. Disease‐causing variants in the collagen‐like tail subunit are the most explained etiology in synaptic CMS, causing defected acetylcholinesterase. In this study whole‐exome sequencing (WES) was performed in an affected boy with muscle weakness, ophthalmoplegia, and bilateral ptosis and gene expression assay by qRT‐PCR was performed in entire family. A homozygous nonsense variant in the COLQ [NM_005677.4:c.679C>T], (p.Arg227Ter) was identified in the proband. Segregation analysis by Sanger sequencing confirmed the homozygous state in the proband and heterozygous state in his parents and four of the siblings. The mRNA expression level in the proband was 0.02 of a healthy person, and in the carriers were 0.42 of a healthy person. This study presents an Iranian family with two affected children and eight symptomatic carriers with attenuated mRNA expression. This study provides evidence that carriers of the COLQ disease‐causing variants could become symptomatic with some yet unknown pathogenesis mechanism and underscore the importance of further investigations to elucidate this mechanism. John Wiley and Sons Inc. 2023-10-23 /pmc/articles/PMC10593973/ /pubmed/37881193 http://dx.doi.org/10.1002/ccr3.8062 Text en © 2023 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Case Report Mohammadi, Mohammad Farid Fateh, Sahand Tehrani Aghajani, Hadi Bahramy, Afshin Zaheryani, Seyed Mohammad Salar Behroozi, Javad Kahani, Seyyed Mohammad Mohammadi, Pouria Garshasbi, Masoud Expression assay of the COLQ in a family with congenital myasthenic syndrome and symptomatic carriers |
title | Expression assay of the COLQ in a family with congenital myasthenic syndrome and symptomatic carriers |
title_full | Expression assay of the COLQ in a family with congenital myasthenic syndrome and symptomatic carriers |
title_fullStr | Expression assay of the COLQ in a family with congenital myasthenic syndrome and symptomatic carriers |
title_full_unstemmed | Expression assay of the COLQ in a family with congenital myasthenic syndrome and symptomatic carriers |
title_short | Expression assay of the COLQ in a family with congenital myasthenic syndrome and symptomatic carriers |
title_sort | expression assay of the colq in a family with congenital myasthenic syndrome and symptomatic carriers |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10593973/ https://www.ncbi.nlm.nih.gov/pubmed/37881193 http://dx.doi.org/10.1002/ccr3.8062 |
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