A Roma founder BIN1 mutation causes a novel phenotype of centronuclear myopathy with rigid spine

Data de publicació: 24/07/2018

Autors de IIS La Fe

Autors aliens a IIS La Fe

Cabrera-Serrano, M
Mavillard, F
Biancalana, V
Rivas, E
Morar, B
Hernandez-Lain, A
Olive, M
Khan, E
Carvajal, A
Quiroga, P
Diaz-Manera, J
Davis, M
Avila, R
Romero, NB
Comas, D
Laing, NG
Laporte, J
Kalaydjieva, L
Paradas, C

Grups d'Investigació

Patología Neuromuscular y Ataxias

Investigador Principal

Teresa Sevilla Mantecón

Abstract

Objective To describe a large series of BIN1 patients, in which a novel founder mutation in the Roma population of southern Spain has been identified. Methods Patients diagnosed with centronuclear myopathy (CNM) at 5 major reference centers for neuromuscular disease in Spain (n = 53) were screened for BIN1 mutations. Clinical, histologic, radiologic, and genetic features were analyzed. Results Eighteen patients from 13 families carried the p.Arg234Cys variant; 16 of them were homozygous for it and 2 had compound heterozygous p.Arg234Cys/p.Arg145Cys mutations. Both BlIV1 variants have only been identified in Roma, causing 100% of CNM in this ethnic group in our cohort. The haplotype analysis confirmed all families are related. In addition to clinical features typical of CNM, such as proximal limb weakness and ophthalmoplegia, most patients in our cohort presented with prominent axial weakness, often associated with rigid spine. Severe fat replacement of paravertebral muscles was demonstrated by muscle imaging. This phenotype seems to be specific to the p.Arg234Cys mutation, not reported in other BIN1 mutations. Extreme clinical variability was observed in the 2 compound heterozygous patients for the p.Arg234Cys/p.Arg145Cys mutations, from a congenital onset with catastrophic outcome to a late-onset disease. Screening of European Roma controls (n = 758) for the p.Arg234Cys variant identified a carrier frequency of 3.5% among the Spanish Roma. Conclusion We have identified a BIN1 founder Roma mutation associated with a highly specific phenotype, which is, from the present cohort, the main cause of CNM in Spain.

Dades de la publicació

ISSN/ISSNe:: 0028-3878, 1526-632X
Tipus:: Article
Pàgines:: 339-348
DOI:: 10.1212/WNL.0000000000005862
PubMed:: 29950440
Factor d'Impacte:: 3,502 SCImago ℠
Quartil:: Q1 SCImago ℠

Documents

No hi ha documents

Mètriques

Filiacions

Cabrera-Serrano, M:: Hosp Univ Virgen del Rocio, Unidad Enfermedades Neuromusculares, Dept Neurol, Seville, Spain

Hosp Univ Virgen del Rocio, Inst Biomed Sevilla IBiS, Seville, Spain
Mavillard, F:: Hosp Univ Virgen del Rocio, Inst Biomed Sevilla IBiS, Seville, Spain
Biancalana, V:: CHRU, Lab Diagnost Genet, Fac Med, Strasbourg, France

IGBMC, Illkirch Graffenstaden, France
Rivas, E:: Hosp Univ Virgen del Rocio, Dept Pathol, Neuropathol Unit, Seville, Spain
Morar, B:: Univ Western Australia, Harry Perkins Inst Med Res, Nedlands, WA, Australia

Univ Western Australia, Med Res Ctr, Nedlands, WA, Australia
Hernandez-Lain, A:: Hosp Univ 12 Octubre, Dept Pathol Neuropathol, Res Inst, Madrid, Spain
Olive, M:: Hosp Bellvitge Princeps Espanya, Neuropathol Unit, Dept Pathol, IDIBELL, Barcelona, Spain

Hosp Bellvitge Princeps Espanya, Neuromuscular Unit, Dept Neurol, IDIBELL, Barcelona, Spain
Muelas, N:: Hosp Univ Politecn La Fe, Dept Neurol, Valencia, Spain

Instituto de Investigación. Hosp Univ Politecn La Fe, IIS La Fe, Valencia, Spain

Hosp Gen Univ Santa Lucia, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Consulta Enfermedades Neuromusculares, Murcia, Spain
Khan, E:: Hosp Gen Univ Santa Lucia, Dept Neurol, Consulta Enfermedades Neuromusculares, Murcia, Spain
Carvajal, A:: Hosp Virgen de las Nieves, Dept Neurol, Granada, Spain
Quiroga, P:: Hosp Torrecardenas, Dept Neurol, Almeria, Spain
Diaz-Manera, J:: Hosp Gen Univ Santa Lucia, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Consulta Enfermedades Neuromusculares, Murcia, Spain

Univ Autonoma Barcelona, Unidad Enfermedades Neuromusculares, Dept Neurol, Hosp Santa Creu & St Pau, Barcelona, Spain
Davis, M:: PathWest Lab Med WA, Dept Diagnost Genom, Perth, WA, Australia
Avila, R:: IGBMC, Illkirch Graffenstaden, France
Dominguez, C:: Hosp 12 Octubre, Dept Neurol, Madrid, Spain
Romero, NB:: Grp Hosp Univ La Pitie Salpetriere, Unite Morphol Neuromusculaire, Ctr Reference Pathol Neuromusculaire Paris Est, Inst Myol, Paris, France

UPMC Univ Paris 06, Univ Sorbonne, Grp Hosp Univ La Pitie Salpetriere, INSERM,UMRS974,CNRS,FRE3617,Ctr Res Myol, Paris, France
Vilchez, JJ:: Hosp Univ Politecn La Fe, Dept Neurol, Valencia, Spain

Instituto de Investigación. Hosp Univ Politecn La Fe, IIS La Fe, Valencia, Spain

Hosp Gen Univ Santa Lucia, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Consulta Enfermedades Neuromusculares, Murcia, Spain

Univ Valencia, Dept Med, Valencia, Spain
Comas, D:: Univ Pompeu Fabra, Dept Expt & Hlth Sci, Inst Evolutionary Biol, CSIC, Barcelona, Spain
Laing, NG:: Univ Western Australia, Harry Perkins Inst Med Res, Nedlands, WA, Australia

Univ Western Australia, Med Res Ctr, Nedlands, WA, Australia
Laporte, J:: IGBMC, Illkirch Graffenstaden, France

CNRS, UMR7104, Illkirch Graffenstaden, France

INSERM, U964, Illkirch Graffenstaden, France
Kalaydjieva, L:: Univ Western Australia, Harry Perkins Inst Med Res, Nedlands, WA, Australia

Univ Western Australia, Med Res Ctr, Nedlands, WA, Australia
Paradas, C:: Hosp Univ Virgen del Rocio, Unidad Enfermedades Neuromusculares, Dept Neurol, Seville, Spain

Hosp Univ Virgen del Rocio, Inst Biomed Sevilla IBiS, Seville, Spain