Abnormalities in alpha-dystroglycan expression in MDC1C and LGMD21 muscular dystrophies
| Autor: | Brown SC, Torelli S, Brockington M, Yuva Y, Jimenez-Mallebrera C, Feng L, Anderson L, Ugo I, Kroger S, Bushby K, Voit T, Sewry C, Muntoni F |
|---|---|
| Rok vydání: | 2004 |
| Zdroj: | AMERICAN JOURNAL OF PATHOLOGY r-FSJD: Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu Fundació Sant Joan de Déu r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu instname |
| ISSN: | 0002-9440 |
| Popis: | We recently identified mutations in the fukutin related protein (FKRP) gene in patients with congenital muscular dystrophy type 1C (MDC1C) and limb girdle muscular dystrophy type 21 (LGMD21). The sarcolemma of these patients typically displays an immunocytochemical reduction of alpha-dystroglycan. in this report we extend these observations and report a clear correlation between the residual expression of alpha-dystroglycan and the phenotype. Three broad categories were identified. Patients at the severe end of the clinical spectrum (MDC1C) were compound heterozygote between a null allele and a missense mutation or carried two missense mutations and displayed a profound depletion of alpha-dystroglycan. Patients with LGMD with a Duchenne-like severity typically had a moderate reduction in alpha-dystroglycan and were compound heterozygotes; between a common C826A (Lcu276Ileu) FKRP mutation and either a missense or a nonsense mutation. Individuals with the milder form of LGMD21 were almost invariably homozygous for the Leu276Ile FKRP mutation and showed a variable but subtle alteration in alpha-dystroglycan immunolabeling. Our data therefore suggest a correlation between a reduction in alpha-dystroglycan, the mutation and the clinical phenotype in MDC1C and LGMD21 which supports the hypothesis that dystroglycan plays a central role in the pathogenesis of these disorders. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|