Phenotypic study in 40 patients with dysferlin gene mutations: high frequency of atypical phenotypes.
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.
Nguyen
Karine
K
Département de Génétique Médicale, Hôpital Timone, Marseille, France. karine.nguyen@ap-hm.fr
Bassez
Guillaume
G
Krahn
Martin
M
Bernard
Rafaelle
R
Laforêt
Pascal
P
Labelle
Véronique
V
Urtizberea
Jon Andoni
JA
Figarella-Branger
Dominique
D
Romero
Norma
N
Attarian
Shahram
S
Leturcq
France
F
Pouget
Jean
J
Lévy
Nicolas
N
Eymard
Bruno
B
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
C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins; D003402:Creatine Kinase