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A Family Case of Congenital Myasthenic Syndrome-22 Induced by Different Combinations of Molecular Causes in Siblings
Congenital myasthenic syndrome-22 (CMS22, OMIM 616224) is a very rare recessive hereditary disorder. At the moment, ten CMS22 patients are described, with the disorder caused by nine different Loss-of-Function mutations and 14 gross deletions in the PREPL gene. The materials for our study were DNA s...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397044/ https://www.ncbi.nlm.nih.gov/pubmed/32707643 http://dx.doi.org/10.3390/genes11070821 |
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author | Shchagina, Olga Bessonova, Ludmila Bychkov, Igor Beskorovainaya, Tatiana Poliakov, Aleksander |
author_facet | Shchagina, Olga Bessonova, Ludmila Bychkov, Igor Beskorovainaya, Tatiana Poliakov, Aleksander |
author_sort | Shchagina, Olga |
collection | PubMed |
description | Congenital myasthenic syndrome-22 (CMS22, OMIM 616224) is a very rare recessive hereditary disorder. At the moment, ten CMS22 patients are described, with the disorder caused by nine different Loss-of-Function mutations and 14 gross deletions in the PREPL gene. The materials for our study were DNA samples of five family members: two patients with myasthenia, their healthy sibling and parents. Clinical exome analysis was carried out for one patient, then the whole family was checked for target variants with Sanger sequencing, quantitative multiplex ligation-dependent probe amplification, and chromosome 2 microsatellite markers study. To determine the functional significance of the splicing variant, we applied the minigene assay. The cause of the proband’s disorder is a compound heterozygous state of two previously non-described pathogenic PREPL variants: a c.1528C>T (p.(Arg510Ter)) nonsense mutation and a c.2094G>T pseudo-missense variant, which, simultaneously with a p.(Lys698Asn) amino acid substitution, affects splicing, leading to exon 14 skipping in mRNA. The second patient’s disorder was caused by a homozygous nonsense c.1528C>T (p.(Arg510Ter)) mutation due to maternal uniparental disomy (UPD) of chromosome 2. In this study, we describe a unique case, in which two siblings with a rare disorder have different pathologic genotypes. |
format | Online Article Text |
id | pubmed-7397044 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-73970442020-08-05 A Family Case of Congenital Myasthenic Syndrome-22 Induced by Different Combinations of Molecular Causes in Siblings Shchagina, Olga Bessonova, Ludmila Bychkov, Igor Beskorovainaya, Tatiana Poliakov, Aleksander Genes (Basel) Brief Report Congenital myasthenic syndrome-22 (CMS22, OMIM 616224) is a very rare recessive hereditary disorder. At the moment, ten CMS22 patients are described, with the disorder caused by nine different Loss-of-Function mutations and 14 gross deletions in the PREPL gene. The materials for our study were DNA samples of five family members: two patients with myasthenia, their healthy sibling and parents. Clinical exome analysis was carried out for one patient, then the whole family was checked for target variants with Sanger sequencing, quantitative multiplex ligation-dependent probe amplification, and chromosome 2 microsatellite markers study. To determine the functional significance of the splicing variant, we applied the minigene assay. The cause of the proband’s disorder is a compound heterozygous state of two previously non-described pathogenic PREPL variants: a c.1528C>T (p.(Arg510Ter)) nonsense mutation and a c.2094G>T pseudo-missense variant, which, simultaneously with a p.(Lys698Asn) amino acid substitution, affects splicing, leading to exon 14 skipping in mRNA. The second patient’s disorder was caused by a homozygous nonsense c.1528C>T (p.(Arg510Ter)) mutation due to maternal uniparental disomy (UPD) of chromosome 2. In this study, we describe a unique case, in which two siblings with a rare disorder have different pathologic genotypes. MDPI 2020-07-19 /pmc/articles/PMC7397044/ /pubmed/32707643 http://dx.doi.org/10.3390/genes11070821 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Brief Report Shchagina, Olga Bessonova, Ludmila Bychkov, Igor Beskorovainaya, Tatiana Poliakov, Aleksander A Family Case of Congenital Myasthenic Syndrome-22 Induced by Different Combinations of Molecular Causes in Siblings |
title | A Family Case of Congenital Myasthenic Syndrome-22 Induced by Different Combinations of Molecular Causes in Siblings |
title_full | A Family Case of Congenital Myasthenic Syndrome-22 Induced by Different Combinations of Molecular Causes in Siblings |
title_fullStr | A Family Case of Congenital Myasthenic Syndrome-22 Induced by Different Combinations of Molecular Causes in Siblings |
title_full_unstemmed | A Family Case of Congenital Myasthenic Syndrome-22 Induced by Different Combinations of Molecular Causes in Siblings |
title_short | A Family Case of Congenital Myasthenic Syndrome-22 Induced by Different Combinations of Molecular Causes in Siblings |
title_sort | family case of congenital myasthenic syndrome-22 induced by different combinations of molecular causes in siblings |
topic | Brief Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397044/ https://www.ncbi.nlm.nih.gov/pubmed/32707643 http://dx.doi.org/10.3390/genes11070821 |
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