Phenotypic heterogeneity in two large Roma families with a congenital myasthenic syndrome due to CHRNE 1267delG mutation. A long-term follow-up

Fecha de publicación: 01/11/2016

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

Natera-de Benito D
Domínguez-Carral J
Nascimento A
Ortez C
Arteaga R
Colomer J

Grupos

Biomedicina Molecular, Celular y Genómica

Leader

José María Millán Salvador
Patología Neuromuscular y Ataxias

Investigador Principal

Teresa Sevilla Mantecón
Unidad mixta de investigación en enfermedades raras (CIPF)

Leader

José María Millán Salvador

Abstract

Congenital myasthenic syndromes (CMS) are a heterogeneous group of genetic disorders. Mutations in CHRNE are one of the most common cause of them and the epsilon 1267delG frameshifting mutation is described to be present on at least one allele of 60% of patients with CHRNE mutations. We present a comprehensive description of the heterogeneous clinical features of the CMS caused by the homozygous 1267delG mutation in the AChR epsilon subunit in nine members of two large Gipsy kindreds. Our observations indicate that founder Roma mutation 1267delG leads to a phenotype further characterized by ophthalmoplegia, bilateral ptosis, and good response to pyridostigmine and 3,4-DAP; but also by facial weakness, bulbar symptoms, neck muscle weakness, and-proximal limb weakness that sometimes entails the loss of ambulation. Interestingly, we found in our series a remarkable proportion of patients with a progressive or fluctuating course of the disease. This finding is in some contrast with previous idea that considered this form of CMS as benign, non progressive, and with a low impact on the capacity of ambulation. (C) 2016 Elsevier B.V. All rights reserved.

Datos de la publicación

ISSN/ISSNe:: 0960-8966, 1873-2364
Tipo:: Article
Páginas:: 789-795
DOI:: 10.1016/j.nmd.2016.08.005
Factor de Impacto:: 1,421 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Métricas

Filiaciones

Natera-de Benito D:: Department of Pediatrics, Hospital Universitario de Fuenlabrada, Madrid, Spain.
Domínguez-Carral J:: Department of Pediatrics, Hospital Universitario Marqués de Valdecilla, Santander, Spain
Muelas N:: Department of Neurology, Hospital Universitari La Fe, Valencia, Spain
Nascimento A:: Department of Neuromuscular Diseases, Hospital Sant Joan de Déu, Barcelona, Spain
Ortez C:: Department of Neuromuscular Diseases, Hospital Sant Joan de Déu, Barcelona, Spain
Jaijo T:: Department of Neurology, Hospital Universitari La Fe, Valencia, Spain
Arteaga R:: Department of Pediatrics, Hospital Universitario Marqués de Valdecilla, Santander, Spain
Colomer J:: Department of Neuromuscular Diseases, Hospital Sant Joan de Déu, Barcelona, Spain
Vilchez JJ:: Department of Neurology, Hospital Universitari La Fe, Valencia, Spain

Keywords

CHRNE; Acetylcholine receptor; Congenital myasthenic syndrome; Congenital myasthenia; Roma gypsies; Neuromuscular junction; Pyridostigmine; 3,4-Diaminopyridine; Founder mutation