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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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”.
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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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