Phenotypic variation in a large Japanese family with Miyoshi myopathy with nonsense mutation in exon 19 of dysferlin gene.
Miyoshi myopathy, an autosomal recessive muscular dystrophy involving distal muscles, is caused by dysferlin mutations. We present clinical and genetic studies of two men and six women, aged 25-83 years, from a Japanese family with consanguineous marriages. Onset was between ages 17 and 59 years. Six of the patients had muscle involvement typical of Miyoshi myopathy, one initially had severe proximal muscle involvement, and one had scapuloperoneal-type muscle involvement. Three patients showed steppage gait. Genetic linkage analysis identified a maximum lod score of 3.34 (&theta;=0.00) at marker D2S292 in 2p13. Analysis of dysferlin revealed the mutation G2090T (Glu573Stop) in exon 19 in all affected patients. This is the largest Japanese family with Miyoshi myopathy showing intrafamilial phenotypic variation and sharing a common mutation in dysferlin.
Nakagawa
M
M
Third Department of Internal Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. nakagawa@m2.kufm.kagoshima-u.ac.jp
Matsuzaki
T
T
Suehara
M
M
Kanzato
N
N
Takashima
H
H
Higuchi
I
I
Matsumura
T
T
Goto
K
K
Arahata
K
K
Osame
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018389:Codon, Nonsense; D004247:DNA / Q000032:analysis / Q000235:genetics; D000073939:Dysferlin; D005091:Exons / Q000235:genetics*; D005190:Family; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D007564:Japan; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D018908:Muscle Weakness / Q000503:physiopathology; D009136:Muscular Dystrophies / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype
D018389:Codon, Nonsense; C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins; D004247:DNA