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Lookup NU author(s): Dr Ana TopfORCiD, Professor Jordi Diaz ManeraORCiD, Dr Nuria Muelas Gomez, Dr Teresinha Evangelista, Dr Yoshiteru Azuma, Dr Grace McMacken, Professor Hanns Lochmuller
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© 2017 Elsevier B.V. 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.
Author(s): Natera-de Benito D, Topf A, Vilchez JJ, Gonzalez-Quereda L, Dominguez-Carral J, Diaz-Manera J, Ortez C, Bestue M, Gallano P, Dusl M, Abicht A, Muller JS, Senderek J, Garcia-Ribes A, Muelas N, Evangelista T, Azuma Y, McMacken G, Paipa Merchan A, Rodriguez Cruz PM, Camacho A, Jimenez E, Miranda-Herrero MC, Santana-Artiles A, Garcia-Campos O, Dominguez-Rubio R, Olive M, Colomer J, Beeson D, Lochmuller H, Nascimento A
Publication type: Article
Publication status: Published
Journal: Neuromuscular Disorders
Year: 2017
Volume: 27
Issue: 12
Pages: 1087-1098
Print publication date: 01/12/2017
Online publication date: 18/08/2017
Acceptance date: 10/08/2017
ISSN (print): 0960-8966
ISSN (electronic): 1873-2364
Publisher: Elsevier Ltd
URL: https://doi.org/10.1016/j.nmd.2017.08.003
DOI: 10.1016/j.nmd.2017.08.003
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