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Congenital Myasthenic Syndrome due to DOK7 mutations in a family from Chile

Congenital myasthenic syndromes (CMS) are neuromuscular transmission disorders caused by mutations in genes encoding neuromuscular junction proteins. A 61-year-old female and her older sister showed bilateral ptosis, facial and proximal limb weakness, and scoliosis since childhood. Another female si...

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Autores principales: Bevilacqua, Jorge A., Lara, Marian, Díaz, Jorge, Campero, Mario, Vázquez, Jessica, Maselli, Ricardo A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PAGEPress Publications, Pavia, Italy 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5658635/
https://www.ncbi.nlm.nih.gov/pubmed/29118959
http://dx.doi.org/10.4081/ejtm.2017.6832
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author Bevilacqua, Jorge A.
Lara, Marian
Díaz, Jorge
Campero, Mario
Vázquez, Jessica
Maselli, Ricardo A.
author_facet Bevilacqua, Jorge A.
Lara, Marian
Díaz, Jorge
Campero, Mario
Vázquez, Jessica
Maselli, Ricardo A.
author_sort Bevilacqua, Jorge A.
collection PubMed
description Congenital myasthenic syndromes (CMS) are neuromuscular transmission disorders caused by mutations in genes encoding neuromuscular junction proteins. A 61-year-old female and her older sister showed bilateral ptosis, facial and proximal limb weakness, and scoliosis since childhood. Another female sibling had milder signs, while other family members were asymptomatic. Facial nerve repetitive stimulation in the proband showed decrement of muscle responses. Single fiber EMG revealed increased jitter and blocking. Muscle biopsy showed type 2-fiber atrophy, without tubular aggregates. Mutational analysis in the three affected siblings revealed two compound heterozygous mutations in DOK7: c.1457delC, that predicts p.Pro486Argfs*13 and truncates the protein C-terminal domain, and c.473G>A, that predicts p.Arg158Gln and disruption of the dok7-MuSK interaction in the phosphotyrosine binding (PTB) domain. Unaffected family members carried only one or neither mutation. Discussion. Two of the affected sisters showed marked improvement with salbutamol treatment, which illustrates the benefits of a correct diagnosis and treatment of DOK7-CMS.
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spelling pubmed-56586352017-11-08 Congenital Myasthenic Syndrome due to DOK7 mutations in a family from Chile Bevilacqua, Jorge A. Lara, Marian Díaz, Jorge Campero, Mario Vázquez, Jessica Maselli, Ricardo A. Eur J Transl Myol Case Report Congenital myasthenic syndromes (CMS) are neuromuscular transmission disorders caused by mutations in genes encoding neuromuscular junction proteins. A 61-year-old female and her older sister showed bilateral ptosis, facial and proximal limb weakness, and scoliosis since childhood. Another female sibling had milder signs, while other family members were asymptomatic. Facial nerve repetitive stimulation in the proband showed decrement of muscle responses. Single fiber EMG revealed increased jitter and blocking. Muscle biopsy showed type 2-fiber atrophy, without tubular aggregates. Mutational analysis in the three affected siblings revealed two compound heterozygous mutations in DOK7: c.1457delC, that predicts p.Pro486Argfs*13 and truncates the protein C-terminal domain, and c.473G>A, that predicts p.Arg158Gln and disruption of the dok7-MuSK interaction in the phosphotyrosine binding (PTB) domain. Unaffected family members carried only one or neither mutation. Discussion. Two of the affected sisters showed marked improvement with salbutamol treatment, which illustrates the benefits of a correct diagnosis and treatment of DOK7-CMS. PAGEPress Publications, Pavia, Italy 2017-09-20 /pmc/articles/PMC5658635/ /pubmed/29118959 http://dx.doi.org/10.4081/ejtm.2017.6832 Text en http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Case Report
Bevilacqua, Jorge A.
Lara, Marian
Díaz, Jorge
Campero, Mario
Vázquez, Jessica
Maselli, Ricardo A.
Congenital Myasthenic Syndrome due to DOK7 mutations in a family from Chile
title Congenital Myasthenic Syndrome due to DOK7 mutations in a family from Chile
title_full Congenital Myasthenic Syndrome due to DOK7 mutations in a family from Chile
title_fullStr Congenital Myasthenic Syndrome due to DOK7 mutations in a family from Chile
title_full_unstemmed Congenital Myasthenic Syndrome due to DOK7 mutations in a family from Chile
title_short Congenital Myasthenic Syndrome due to DOK7 mutations in a family from Chile
title_sort congenital myasthenic syndrome due to dok7 mutations in a family from chile
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5658635/
https://www.ncbi.nlm.nih.gov/pubmed/29118959
http://dx.doi.org/10.4081/ejtm.2017.6832
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