Résumé :
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Facioscapulohumeral muscular dystrophy (FSHD) is linked in more than 95% of cases to D4Z4 repeat contraction on chromosome 4q35 (FSHD1). In patients with a typical clinical presentation but without D4Z4 repeat deletions, loss of DNA methylation can be the cause. These patients are defined as FSHD2. We retrospectively identified patients with FSHD2 from our registry and described their phenotype. Ninety-nine out of 108 patients with a clinical diagnosis of FSHD carried the D4Z4 deletion. For seven patients without a D4Z4 deletion we repeated genetic analysis. The repeat sizes and methylation levels of the D4Z4 arrays were tested on both chromosome 4q alleles and chromosome 10q alleles by Southern blot analysis. For chromosome 4q three different CpG dinucleotides were studied with three methylationsensitive restriction enzymes (BsaAI, FseI, CpoI) and for chromosome 10q CpoI was used.In one patient (1/7) we confirmed FSHD1. Three (3/7) patients were potentially FSHD2. They represented 3% from all patients with a FSHD phenotype. Three (3/7) patients were neither FSHD1 nor FSHD2. All three patients with potential FSHD2 were sporadic cases. In two patients the first symptoms were facial and shoulder weakness, while in the third patient it was knee extension weakness. The disease started on average at the age of 40 years. During the disease course all patients developed asymmetric shoulder girdle weakness, two facial, two upper arm, one abdominal, two foot dorsiflexors' and all three pelvic girdle muscle weakness. One patient had asymmetry in orbicularis oris. None had weakness of the external ocular muscles, dysphagia, tongue weakness or hearing loss. One patient had arrhythmia but no cardiomyopathy. One patient had 16-times increased serum CK activity, while in the other two patients the increase was only mild. All had myopathic EMG and non-specific myopathic changes in muscle biopsy. The disease was slowly progressive, but one patient became wheelchair bound. Two patients fulfilled the FSHD clinical criteria (European Neuromuscular Centre, 1997), while in one patient the pattern is more of asymmetric involvement of limb-girdle.In conclusion, the phenotype of potential FSHD2 seems indistinguishable from FSHD1.
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