Clinical heterogeneity in dysferlinopathy.
OBJECTIVE
To clarify the clinical heterogeneity and genotype-phenotype correlation in dysferlinopathy.


METHODS
We evaluated clinical parameters of 74 dysferlinopathy patients with known dysferlin gene mutations who were previously reported in the literature.


RESULTS
The age at onset varied from 12 to 59 years (mean 21.7 years). Based on the initial distribution of muscle involvement, clinical phenotypes were divided into four subtypes: limb-girdle type, Miyoshi's type, distal anterior compartment type, or scapuloperoneal type. These phenotypic differences were prominent at the early stages, but were difficult to recognize later in the progression of the disease. Patients with missense mutations had significantly more severe functional status at examination and higher creatine kinase levels than those with frameshift or nonsense mutations.


CONCLUSIONS
Dysferlinopathy exhibited marked heterogeneity in the age at onset, initial distribution of muscle involvement, and rate of disease progression. As this heterogeneity was observed even within the same family, some additional factors distinct from dysferlin might be involved.
Ueyama
Hidetsugu
H
Third Department of Internal Medicine, Oita Medical University.
Kumamoto
Toshihide
T
Horinouchi
Hideo
H
Fujimoto
Shin
S
Aono
Hiroshi
H
Tsuda
Tomiyasu
T
D000293:Adolescent; D000328:Adult; D002648:Child; D003402:Creatine Kinase / Q000097:blood / Q000235:genetics; D000073939:Dysferlin; D004576:Electromyography; D005260:Female; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D018482:Muscle, Skeletal; D009136:Muscular Dystrophies / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D009154:Mutation / Q000235:genetics; D010641:Phenotype; 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