Dysferlin mutation analysis in a group of Italian patients with limb-girdle muscular dystrophy and Miyoshi myopathy.
Mutations in the dysferlin gene (DYSF) on chromosome 2p13 cause distinct phenotypes of muscular dystrophy: limb-girdle muscular dystrophy type 2B (LGMD2B), Miyoshi myopathy (MM), and distal anterior compartment myopathy, which are known by the term 'dysferlinopathy'. We performed mutation analyses of DYSF in 14 Italian patients from 10 unrelated families with a deficiency of dysferlin protein below 20% of the value in normal controls by immunoblotting analysis. We identified 11 different mutations, including eight missense and three deletion mutations. Nine of them were novel mutations. We also identified a unique 6-bp insertion polymorphism within the coding region of DYSF in 15% of Italian population, which was not observed in East Asian populations. The correlation between clinical phenotype and the gene mutations was unclear, which suggested the role of additional genetic and epigenetic factors in modifying clinical symptoms.
Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan.
K
K
Kawabe
K
K
Goto
I
I
Nishino
C
C
Angelini
Y K
YK
Hayashi
D000293:Adolescent; D000328:Adult; D004252:DNA Mutational Analysis / Q000379:methods; D000073939:Dysferlin; D005091:Exons; D005260:Female; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D007558:Italy / Q000453:epidemiology / Q000208:ethnology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D049288:Muscular Dystrophies, Limb-Girdle / Q000150:complications / Q000235:genetics*; D009154:Mutation; D044468:Native Hawaiian or Pacific Islander / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods
C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins