title: Phenotypic study in 40 patients with dysferlin gene mutations: high frequency of atypical phenotypes.
abstract: 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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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: Département de Génétique Médicale, Hôpital Timone, Marseille, France. karine.nguyen@ap-hm.fr
authors: Karine
authors: K
authors: Nguyen
authors: Guillaume
authors: G
authors: Bassez
authors: Martin
authors: M
authors: Krahn
authors: Rafaelle
authors: R
authors: Bernard
authors: Pascal
authors: P
authors: Laforêt
authors: Véronique
authors: V
authors: Labelle
authors: Jon Andoni
authors: JA
authors: Urtizberea
authors: Dominique
authors: D
authors: Figarella-Branger
authors: Norma
authors: N
authors: Romero
authors: Shahram
authors: S
authors: Attarian
authors: France
authors: F
authors: Leturcq
authors: Jean
authors: J
authors: Pouget
authors: Nicolas
authors: N
authors: Lévy
authors: Bruno
authors: B
authors: Eymard
mesh_terms: D000328:Adult; D000368:Aged; D001132:Arm; D003402:Creatine Kinase / Q000097:blood; D003951:Diagnostic Errors; D018450:Disease Progression; D000073939:Dysferlin; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics*; D008875:Middle Aged; D009124:Muscle Proteins / Q000172:deficiency / Q000235:genetics*; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging / Q000473:pathology; D009136:Muscular Dystrophies / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D049288:Muscular Dystrophies, Limb-Girdle / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D010641:Phenotype; D017285:Polymyositis / Q000175:diagnosis; D012189:Retrospective Studies; D012720:Severity of Illness Index; D014057:Tomography, X-Ray Computed
chemical_list: C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins; D003402:Creatine Kinase