• Karine Nguyen, Guillaume Bassez, Martin Krahn, Rafaelle Bernard, Pascal Laforêt, Véronique Labelle, Jon Andoni Urtizberea, Dominique Figarella-Branger, Norma Romero, Shahram Attarian, France Leturcq, Jean Pouget, Nicolas Lévy, and Bruno Eymard.
• Département de Génétique Médicale, Hôpital Timone, Marseille, France. karine.nguyen@ap-hm.fr
• Arch Neurol Chicago. 2007 Aug 1; 64 (8): 1176-82.

ObjectiveTo describe the phenotypic spectrum of dysferlin (DYSF) gene mutations (which cause dysferlinopathies, autosomal recessive muscular dystrophies) in patients with a dysferlin protein deficiency.DesignClinical, biological, and pathological data from 40 patients were reviewed. The diagnosis of dysferlinopathy was based on the absence or strong reduction of dysferlin in muscle, and confirmed by mutational screening of the DYSF gene.SettingTwo French neuromuscular diseases centers (in Paris and Marseilles).ResultsTwo main dysferlinopathy phenotypes are well recognized: Miyoshi myopathy and limb-girdle muscular dystrophy type 2B. Typical Miyoshi myopathy and limb-girdle muscular dystrophy type 2B were found in 20 (50%) patients only. Unusual phenotypes included a mixed phenotype, referred to as "proximodistal," combining distal and proximal onset in 14 (35%) patients, pseudometabolic myopathy in 4 (10%), and asymptomatic hyperCKemia (an increased serum creatine kinase level) in 2 (5%). The disease may worsen rapidly, and 10 (25%) patients were initially misdiagnosed as having polymyositis. We suggest a relationship between proximodistal phenotype, inflammation, and severity.ConclusionIn addition to typical Miyoshi myopathy and limb-girdle muscular dystrophy type 2B, dysferlinopathies are a clinically heterogeneous group of disorders ranging from asymptomatism to severe functional disability.

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