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Abnormalities in alpha-dystroglycan expression in MDC1C and LGMD21 muscular dystrophies

Brown, SC; Torelli, S; Brockington, M; Yuva, Y; Jimenez, C; Feng, L; Anderson, L; ... Muntoni, F; + view all (2004) Abnormalities in alpha-dystroglycan expression in MDC1C and LGMD21 muscular dystrophies. AM J PATHOL , 164 (2) 727 - 737.

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Abstract

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.

Type: Article
Title: Abnormalities in alpha-dystroglycan expression in MDC1C and LGMD21 muscular dystrophies
Keywords: FUKUTIN-RELATED PROTEIN, EXTRACELLULAR-MATRIX, GLYCOPROTEIN COMPLEX, SKELETAL-MUSCLE, MOLECULAR PATHOGENESIS, SARCOGLYCAN COMPLEX, LAMININ, DEFICIENCY, MEMBRANE, DISRUPTION
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH Developmental Neurosciences Prog
URI: http://discovery.ucl.ac.uk/id/eprint/146283
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