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The First Case of Congenital Myasthenic Syndrome Caused by a Large Homozygous Deletion in the C-Terminal Region of COLQ (Collagen Like Tail Subunit of Asymmetric Acetylcholinesterase) Protein
Congenital myasthenic syndromes (CMSs) are caused by mutations in genes that encode proteins involved in the organization, maintenance, function, or modification of the neuromuscular junction. Among these, the collagenic tail of endplate acetylcholinesterase protein (COLQ; MIM 603033) has a crucial...
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/PMC7765904/ https://www.ncbi.nlm.nih.gov/pubmed/33353066 http://dx.doi.org/10.3390/genes11121519 |
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author | Laforgia, Nicola De Cosmo, Lucrezia Palumbo, Orazio Ranieri, Carlotta Sesta, Michela Capodiferro, Donatella Pantaleo, Antonino Iapicca, Pierluigi Lastella, Patrizia Capozza, Manuela Schettini, Federico Bukvic, Nenad Bagnulo, Rosanna Resta, Nicoletta |
author_facet | Laforgia, Nicola De Cosmo, Lucrezia Palumbo, Orazio Ranieri, Carlotta Sesta, Michela Capodiferro, Donatella Pantaleo, Antonino Iapicca, Pierluigi Lastella, Patrizia Capozza, Manuela Schettini, Federico Bukvic, Nenad Bagnulo, Rosanna Resta, Nicoletta |
author_sort | Laforgia, Nicola |
collection | PubMed |
description | Congenital myasthenic syndromes (CMSs) are caused by mutations in genes that encode proteins involved in the organization, maintenance, function, or modification of the neuromuscular junction. Among these, the collagenic tail of endplate acetylcholinesterase protein (COLQ; MIM 603033) has a crucial role in anchoring the enzyme into the synaptic basal lamina. Here, we report on the first case of a patient with a homozygous deletion affecting the last exons of the COLQ gene in a CMS patient born to consanguineous parents of Pakistani origin. Electromyography (EMG), electroencephalography (EEG), clinical exome sequencing (CES), and single nucleotide polymorphism (SNP) array analyses were performed. The subject was born at term after an uneventful pregnancy and developed significant hypotonia and dystonia, clinical pseudoseizures, and recurring respiratory insufficiency with a need for mechanical ventilation. CES analysis of the patient revealed a homozygous deletion of the COLQ gene located on the 3p25.1 chromosome region. The SNP-array confirmed the presence of deletion that extended from exon 11 to the last exon 17 with a size of 19.5 Kb. Our results add new insights about the underlying pathogenetic mechanisms expanding the spectrum of causative COLQ mutations. It is relevant, considering the therapeutic implications, to apply suitable molecular approaches so that no type of mutation is missed: “each lost mutation means a baby treated improperly”. |
format | Online Article Text |
id | pubmed-7765904 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77659042020-12-28 The First Case of Congenital Myasthenic Syndrome Caused by a Large Homozygous Deletion in the C-Terminal Region of COLQ (Collagen Like Tail Subunit of Asymmetric Acetylcholinesterase) Protein Laforgia, Nicola De Cosmo, Lucrezia Palumbo, Orazio Ranieri, Carlotta Sesta, Michela Capodiferro, Donatella Pantaleo, Antonino Iapicca, Pierluigi Lastella, Patrizia Capozza, Manuela Schettini, Federico Bukvic, Nenad Bagnulo, Rosanna Resta, Nicoletta Genes (Basel) Case Report Congenital myasthenic syndromes (CMSs) are caused by mutations in genes that encode proteins involved in the organization, maintenance, function, or modification of the neuromuscular junction. Among these, the collagenic tail of endplate acetylcholinesterase protein (COLQ; MIM 603033) has a crucial role in anchoring the enzyme into the synaptic basal lamina. Here, we report on the first case of a patient with a homozygous deletion affecting the last exons of the COLQ gene in a CMS patient born to consanguineous parents of Pakistani origin. Electromyography (EMG), electroencephalography (EEG), clinical exome sequencing (CES), and single nucleotide polymorphism (SNP) array analyses were performed. The subject was born at term after an uneventful pregnancy and developed significant hypotonia and dystonia, clinical pseudoseizures, and recurring respiratory insufficiency with a need for mechanical ventilation. CES analysis of the patient revealed a homozygous deletion of the COLQ gene located on the 3p25.1 chromosome region. The SNP-array confirmed the presence of deletion that extended from exon 11 to the last exon 17 with a size of 19.5 Kb. Our results add new insights about the underlying pathogenetic mechanisms expanding the spectrum of causative COLQ mutations. It is relevant, considering the therapeutic implications, to apply suitable molecular approaches so that no type of mutation is missed: “each lost mutation means a baby treated improperly”. MDPI 2020-12-18 /pmc/articles/PMC7765904/ /pubmed/33353066 http://dx.doi.org/10.3390/genes11121519 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 | Case Report Laforgia, Nicola De Cosmo, Lucrezia Palumbo, Orazio Ranieri, Carlotta Sesta, Michela Capodiferro, Donatella Pantaleo, Antonino Iapicca, Pierluigi Lastella, Patrizia Capozza, Manuela Schettini, Federico Bukvic, Nenad Bagnulo, Rosanna Resta, Nicoletta The First Case of Congenital Myasthenic Syndrome Caused by a Large Homozygous Deletion in the C-Terminal Region of COLQ (Collagen Like Tail Subunit of Asymmetric Acetylcholinesterase) Protein |
title | The First Case of Congenital Myasthenic Syndrome Caused by a Large Homozygous Deletion in the C-Terminal Region of COLQ (Collagen Like Tail Subunit of Asymmetric Acetylcholinesterase) Protein |
title_full | The First Case of Congenital Myasthenic Syndrome Caused by a Large Homozygous Deletion in the C-Terminal Region of COLQ (Collagen Like Tail Subunit of Asymmetric Acetylcholinesterase) Protein |
title_fullStr | The First Case of Congenital Myasthenic Syndrome Caused by a Large Homozygous Deletion in the C-Terminal Region of COLQ (Collagen Like Tail Subunit of Asymmetric Acetylcholinesterase) Protein |
title_full_unstemmed | The First Case of Congenital Myasthenic Syndrome Caused by a Large Homozygous Deletion in the C-Terminal Region of COLQ (Collagen Like Tail Subunit of Asymmetric Acetylcholinesterase) Protein |
title_short | The First Case of Congenital Myasthenic Syndrome Caused by a Large Homozygous Deletion in the C-Terminal Region of COLQ (Collagen Like Tail Subunit of Asymmetric Acetylcholinesterase) Protein |
title_sort | first case of congenital myasthenic syndrome caused by a large homozygous deletion in the c-terminal region of colq (collagen like tail subunit of asymmetric acetylcholinesterase) protein |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765904/ https://www.ncbi.nlm.nih.gov/pubmed/33353066 http://dx.doi.org/10.3390/genes11121519 |
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