Résumé :
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Recessive mutations in anoctamin 5 (ANO5) have recently been identified in two distinct phenotypes, limb-girdle muscular dystrophy (LGMD) or distal non-dysferlin Miyoshi-like dystrophy (MMD3). The clinical features have consisted of adult onset slowly progressive myopathy, which involves mainly the pelvic girdle and proximal lower limbs or more rarely distal lower limbs. Hands are usually not affected and respiratory or cardiac involvement has not been reported. The patients typically have very high CK levels.Seventy Finnish patients with high CK levels and myopathy with unknown etiology were screened for ANO5 mutations. The only selection criterion was CK level over 3000 in undiagnosed patients. The most common mutation in Europe (c.191dupA (p.N64KfsX15)) and the mutation found most frequently in Finland (c.2272C>T (p.R758C)) were tested. 15 patients (21 %) had either of the screened mutations. Clinical phenotype of these patients varied from exercise myalgia and calf hypertrophy to proximal myopathy with the mean age of onset 24 y. There were six female and nine male patients. Only one of the female patients had mild proximal lower limb weakness while five others had no clinically detectable weakness, despite clear dystrophic changes in muscle MRI. Male patients had more pronounced LGMD (7/9) or distal calf dystrophy (2/9). No phenotype was restricted to a certain mutational background and both of the frequent mutations were associated with mild to more severe involvement as well as distal, proximal or proximodistal phenotypes. The levels of CK did not correlate with the severity of symptoms (range 1000-20000).Previously, it has been suggested that mutations in ANO5, especially the common c.191dupA, result in a homogeneous clinical presentation. In our cohort, the clinical phenotype was heterogeneous and the severity of symptoms varied extensively between patients even with the same mutation. The only common clue to diagnosis was a very high CK level.
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