Academic Journal
LGMD2A: genotype-phenotype correlations based on a large mutational survey on the calpain 3 gene
| العنوان: | LGMD2A: genotype-phenotype correlations based on a large mutational survey on the calpain 3 gene |
|---|---|
| المؤلفون: | Sáenz, A., Leturcq, F., Cobo, A. M., Poza, J. J., Ferrer, X., Otaegui, D., Camaño, P., Urtasun, M., Vílchez, J., Gutiérrez-Rivas, E., Emparanza, J., Merlini, L., Paisán, C., Goicoechea, M., Blázquez, L., Eymard, B., Lochmuller, H., Walter, M., Bonnemann, C., Figarella-Branger, D., Kaplan, J. C., Urtizberea, J. A., Martí-Massó, J. F., de Munain, A. López |
| بيانات النشر: | Oxford University Press |
| سنة النشر: | 2005 |
| المجموعة: | HighWire Press (Stanford University) |
| مصطلحات موضوعية: | Articles |
| الوصف: | We present here the clinical, molecular and biochemical findings from 238 limb-girdle muscular dystrophy type 2A (LGMD2A) patients, representing ∼50% (238 out of 484) of the suspected calpainopathy cases referred for the molecular study of the calpain 3 ( CAPN3 ) gene. The mean age at onset of LGMD2A patients was ∼14 years, and the first symptoms occurred between 6 and 18 years of age in 71% of patients. The mean age at which the patients became wheelchair bound was 32.2 years, with 84% requiring the use of a wheelchair between the age of 21 and 40 years. There was no correlation between the age at onset and the time at which the patient became wheelchair bound, nor between the sex of the patient and the risk of becoming wheelchair bound. Of the cases where the CAPN3 gene was not affected, ∼20% were diagnosed as LGMD2I muscular dystrophy, while facioscapulohumeral muscular dystrophy (FSHD) was uncommon in this sample. We identified 105 different mutations in the CAPN3 gene of which 50 have not been described previously. These were distributed throughout the coding region of the gene, although some exons remained free of mutations. The most frequent mutation was 2362AG→TCATCT (exon 22), which was present in 30.7% of the chromosomes analysed (146 chromosomes). Other recurrent mutations described were N50S, 550ΔA, G222R, IVS6-1G→A, A483D, IVS17+1G→T, 2069–2070ΔAC, R748Q and R748X, each of which was found in >5 chromosomes. The type of mutation in the CAPN3 gene does not appear to be a risk factor for becoming dependent on a wheelchair at a determined age. However, in the cases with two null mutations, there were significantly fewer patients that were able to walk than in the group of patients with at least one missense mutation. Despite the fact that the results of phenotyping and western blot might be biased due to multiple referral centres, producing a diagnosis on the basis of the classical phenotype is neither sufficiently sensitive (86.7%) nor specific (69.3%), although western blot proved to be even less ... |
| نوع الوثيقة: | text |
| وصف الملف: | text/html |
| اللغة: | English |
| Relation: | http://brain.oxfordjournals.org/cgi/content/short/128/4/732; http://dx.doi.org/10.1093/brain/awh408 |
| DOI: | 10.1093/brain/awh408 |
| الاتاحة: | http://brain.oxfordjournals.org/cgi/content/short/128/4/732 https://doi.org/10.1093/brain/awh408 |
| Rights: | Copyright (C) 2005, Oxford University Press |
| رقم الانضمام: | edsbas.CB4165E1 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/brain/awh408 |
|---|