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Molecular characterization of congenital myasthenic syndromes in Spain.

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Autores de IDIVAL

Autores ajenos al IDIVAL

  • Natera-de Benito D
  • Töpf A
  • Vilchez JJ
  • González-Quereda L
  • Díaz-Manera J
  • Ortez C
  • Bestué M
  • Gallano P
  • Dusl M
  • Abicht A
  • Müller JS
  • Senderek J
  • García-Ribes A
  • Muelas N
  • Evangelista T
  • Azuma Y
  • McMacken G
  • Paipa Merchan A
  • Rodríguez Cruz PM
  • Camacho A
  • Jiménez E
  • Miranda-Herrero MC
  • Santana-Artiles A
  • García-Campos O
  • Dominguez-Rubio R
  • Olivé M
  • Colomer J
  • Beeson D
  • Lochmüller H
  • Nascimento A

Unidades

Abstract

Congenital myasthenic syndromes (CMS) are a heterogeneous group of genetic disorders, all of which impair neuromuscular transmission. Epidemiological data and frequencies of gene mutations are scarce in the literature. Here we describe the molecular genetic and clinical findings of sixty-four genetically confirmed CMS patients from Spain. Thirty-six mutations in the CHRNE, RAPSN, COLQ, GFPT1, DOK7, CHRNG, GMPPB, CHAT, CHRNA1, and CHRNB1 genes were identified in our patients, with five of them not reported so far. These data provide an overview on the relative frequencies of the different CMS subtypes in a large Spanish population. CHRNE mutations are the most common cause of CMS in Spain, accounting for 27% of the total. The second most common are RAPSN mutations. We found a higher rate of GFPT1 mutations in comparison with other populations. Remarkably, several founder mutations made a large contribution to CMS in Spain: RAPSN c.264C A (p.Asn88Lys), CHRNE c.130insG (Glu44Glyfs*3), CHRNE c.1353insG (p.Asn542Gluf*4), DOK7 c.1124_1127dup (p.Ala378Serfs*30), and particularly frequent in Spain in comparison with other populations, COLQ c.1289A C (p.Tyr430Ser). Furthermore, we describe phenotypes and distinguishing clinical signs associated with the various CMS genes which might help to identify specific CMS subtypes to guide diagnosis and management.

Copyright © 2017 Elsevier B.V. All rights reserved.

Datos de la publicación

ISSN/ISSNe:
0960-8966, 1873-2364

NEUROMUSCULAR DISORDERS  PERGAMON-ELSEVIER SCIENCE LTD

Tipo:
Article
Páginas:
1087-1098
PubMed:
29054425

Citas Recibidas en Web of Science: 56

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Keywords

  • CHRNE, COLQ, Congenital myasthenic syndrome, DOK7, GFPT1, GMPPB, Genetic mutations, RAPSN, Slow-channel syndrome

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