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Molecular characterization of congenital myasthenic syndromes in Spain

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.

Publication metadata

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


DOI: 10.1016/j.nmd.2017.08.003


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