RT Journal Article
T1 A Roma founder BIN1 mutation causes a novel phenotype of centronuclear myopathy with rigid spine.
A1 Cabrera-Serrano, Macarena
A1 Mavillard, Fabiola
A1 Biancalana, Valerie
A1 Rivas, Eloy
A1 Morar, Bharti
A1 Hernández-Laín, Aurelio
A1 Olive, Montse
A1 Muelas, Nuria
A1 Khan, Eduardo
A1 Carvajal, Alejandra
A1 Quiroga, Pablo
A1 Diaz-Manera, Jordi
A1 Davis, Mark
A1 Ávila, Rainiero
A1 Domínguez, Cristina
A1 Romero, Norma Beatriz
A1 Vílchez, Juan J
A1 Comas, David
A1 Laing, Nigel G
A1 Laporte, Jocelyn
A1 Kalaydjieva, Luba
A1 Paradas, Carmen
AB To describe a large series of BIN1 patients, in which a novel founder mutation in the Roma population of southern Spain has been identified. 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. 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 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. 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.
YR 2018
FD 2018-06-27
LK https://hdl.handle.net/10668/28323
UL https://hdl.handle.net/10668/28323
LA en
DS RISalud
RD Apr 10, 2025