Abstract:
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BACKGROUNDFacioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant myopathy associated with contraction of the subtelomeric D4Z4 repeat array on chromosome 4q.Two allelic variations of 4qter have been described. These variations, 4qA and 4qB, differ by a few insertion and deletion polymorphisms distal to D4Z. It has been reported that FSHD disease alleles are exclusively of the 4qA type.There is a marked inter and intra-familial heterogeneity in its clinical expression which probably depend on multiple genetic and environmental factors unknown yet.Little is known about the spectrum of clinical expression and the genotype-phenotype correlations of the small deletions (large fragments or borderline D4Z4 repeat size from 7 to 10 units (U). OBJECTIVETo test the correlation between clinical severity and fragment size in FSHD patients with a fragment size > 7U.To study the heterogeneity of clinical expression by studying the size of D4Z4 repeat on the non deleted allele PATIENTS AND METHODSWe prospectively analysed a multicentric cohort of patientswith a clinical and genetically supported diagnosis of FSHD, carrying a D4Z4 repeat of 7 to 10 U. Patients were assessed by a standardized clinical examination, manual muscle testing, MFM scale, Brooke and Vignos scale, Gardner-Medwin and Walton scale, ten-meter walk test, 4-steps and self-assessment of physical activity. Genetic analysis were performed.Pulsed field gel electrophoresis (PFGE) and conventional gel electrophoresis have been used to determine the size and chromosomal origin (chromosome 4 or 10) of each of the fragments. The DNA have been double digested with EcoRI and EcoRI/BlnI. It will be separated and transferred to membrane by Southern Blotting and hybridized with probe p13E11 labeled with P32 dCTP. To study allelic variations of 4qter we used two other probes: 4qA and 4qB. RESULTS67 patients (22 women, 45 men) were included (mean age, 51 years(± 15)).Mean age at onset was 30 years(± 17). Mean duration of the disease was 6,5 (± 4.8).Number of D4Z4 repeated units was distributed as follow: 52,3% with 7U, 17,9% with 8U,13,4% with 9 U, 10,5% with 11 UR and 1,5%. with11UR.DISCUSSIONAnalysis are ongoing. The results of different correlations between phenotype and genotype will be presented."The study was supported by AFM."
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