OBJECTIVE: To describe the phenotypic spectrum of dysferlin (DYSF) gene mutations (which cause dysferlinopathies, autosomal recessive muscular dystrophies) in patients with a dysferlin protein deficiency. DESIGN: Clinical, 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. SETTING: Two French neuromuscular diseases centers (in Paris and Marseilles). RESULTS: Two 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. CONCLUSION: In 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.
OBJECTIVE: To describe the phenotypic spectrum of dysferlin (DYSF) gene mutations (which cause dysferlinopathies, autosomal recessive muscular dystrophies) in patients with a dysferlin protein deficiency. DESIGN: Clinical, 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. SETTING: Two French neuromuscular diseases centers (in Paris and Marseilles). RESULTS: Two 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. CONCLUSION: In 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.
Authors: Joseph J Belanto; Silvia V Diaz-Perez; Clara E Magyar; Michele M Maxwell; Yasemin Yilmaz; Kasey Topp; Guney Boso; Catriona H Jamieson; Nicholas A Cacalano; Christina A M Jamieson Journal: Neuromuscul Disord Date: 2010-01-18 Impact factor: 4.296
Authors: Kanneboyina Nagaraju; Rashmi Rawat; Edina Veszelovszky; Rachana Thapliyal; Akanchha Kesari; Susan Sparks; Nina Raben; Paul Plotz; Eric P Hoffman Journal: Am J Pathol Date: 2008-02-14 Impact factor: 4.307
Authors: Yen-Hui Chiu; Mark A Hornsey; Lars Klinge; Louise H Jørgensen; Steven H Laval; Richard Charlton; Rita Barresi; Volker Straub; Hanns Lochmüller; Kate Bushby Journal: Hum Mol Genet Date: 2009-03-13 Impact factor: 6.150