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A Roma founder BIN1 mutation causes a novel phenotype of centronuclear myopathy with rigid spine
- Source :
- Neurology, Neurology, American Academy of Neurology, 2018, 91 (4), pp.339-348. ⟨10.1212/WNL.0000000000005862⟩, Neurology, 2018, 91 (4), pp.339-348. ⟨10.1212/WNL.0000000000005862⟩, NEUROLOGY, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, instname, r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe
- Publication Year :
- 2018
- Publisher :
- HAL CCSD, 2018.
-
Abstract
- ObjectiveTo describe a large series of BIN1 patients, in which a novel founder mutation in the Roma population of southern Spain has been identified.MethodsPatients 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.ResultsEighteen 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 BIN1 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.ConclusionWe 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.
- Subjects :
- Adult
0301 basic medicine
medicine.medical_specialty
Roma
Neuromuscular disease
Adolescent
Population
Mallory Bodies
Compound heterozygosity
Article
Muscular Dystrophies
Cohort Studies
Young Adult
03 medical and health sciences
0302 clinical medicine
Internal medicine
medicine
Humans
Prospective Studies
Centronuclear myopathy
Child
education
Prospective cohort study
Adaptor Proteins, Signal Transducing
Retrospective Studies
education.field_of_study
business.industry
Tumor Suppressor Proteins
Haplotype
Nuclear Proteins
Retrospective cohort study
Middle Aged
medicine.disease
Founder Effect
Phenotype
030104 developmental biology
Scoliosis
Spain
Mutation
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Neurology (clinical)
business
030217 neurology & neurosurgery
Myopathies, Structural, Congenital
Founder effect
Subjects
Details
- Language :
- English
- ISSN :
- 00283878 and 1526632X
- Database :
- OpenAIRE
- Journal :
- Neurology, Neurology, American Academy of Neurology, 2018, 91 (4), pp.339-348. ⟨10.1212/WNL.0000000000005862⟩, Neurology, 2018, 91 (4), pp.339-348. ⟨10.1212/WNL.0000000000005862⟩, NEUROLOGY, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, instname, r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe
- Accession number :
- edsair.doi.dedup.....e213788b7dc0c1c6ee86bdb461641667