A Dutch cohort of 105 limb girdle muscular dystrophy (LGMD) patients were subject to subsequent genetic investigations. In half the
families a causative mutation was found. Recently mutations were identified in ANO5 causing LGMD2L and Miyoshi-like myopathy
(MMD3), but could also be found in patients with hyperCKemia only. Therefore, we analysed the index cases of the remaining 31 as
yet undiagnosed families from our previously described cohort of LGMD patients for the presence of ANO5 mutations. Detailed
history and neurological examination were available for all patients. Serum creatine kinase (CK) activity, skeletal muscle computed
tomography (CT) and cardiological investigations were performed. Mutations in ANO5 were found in 16% of the families: 11 index
patients and two sibs, eight males and five females. The founder mutation c.191dupA was present in 8 out of 13 patients. Ten
different pathogenic mutations were identified of which seven were novel: five missense and two splice site mutations. The age of
these patients ranged from 26 to 69 years and the age of onset varied from 21 to 57 years. Symptoms at onset were related to
proximal leg weakness. The weakness was slowly progressive. Calf hypertrophy was present in three patients. Males were more
severely affected than females. Serum CK activity was highly elevated in the early stage of disease and moderately increased in later
stages. Muscle biopsy showed predominantly dystrophic changes. One patient had hypertrophic cardiomyopathy, two others had
intraventricular septum thickening.
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