Novel DYSF mutations in Thai patients with distal myopathy.
Dysferlinopathy refers to a variety of autosomal recessive, skeletal muscle disorders due to the mutations of dysferlin-encoding gene, DYSF. It encompasses limb-girdle muscular dystrophy type 2B (LGMD2B), Miyoshi myopathy (MM), distal myopathy with anterior tibial onset (DMAT), isolated hyperCKemia, rigid spine syndrome and congenital muscular dystrophy. Herein, we report five Thai patients with distal myopathy due to dysferlinopathy including four MM and one DMAT patients. Muscle biopsy from one MM patient depicted numerous ring fibers which is an atypical finding in dysferlinopathy. Mutation analysis of DYSF revealed novel compound heterozygous mutations of p.Tyr309X and c.236+1G>T in two related MM patients, known homozygous mutations, p.Arg89X and p.Gln176X, in two MM patients and a heterozygous missense mutation, p.Arg555Trp, in a DMAT patient. Most of the previously reported DMAT patients were Hispanic. To the best of our knowledge, this is the first report of genetically confirmed patients with dysferlinopathy in Thailand.
Liewluck
Teerin
T
Division of Neuropathology, Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok-Noi, Bangkok 10700, Thailand. sitll@mahidol.ac.th
Pongpakdee
Sunsanee
S
Witoonpanich
Rawiphan
R
Sangruchi
Tumtip
T
Pho-Iam
Theeraphong
T
Limwongse
Chanin
C
Thongnoppakhun
Wanna
W
Boonyapisit
Kanokwan
K
Sopassathit
Varisa
V
Phudhichareonrat
Suchart
S
Suthiponpaisan
Udom
U
Raksadawan
Natte
N
Goto
Kanako
K
Hayashi
Yukiko K
YK
Nishino
Ichizo
I
D000328:Adult; D015153:Blotting, Western; D003402:Creatine Kinase / Q000097:blood; D049310:Distal Myopathies / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D000073939:Dysferlin; D005091:Exons / Q000235:genetics; D005190:Family; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007438:Introns / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation / Q000502:physiology; D011110:Polymorphism, Genetic / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013785:Thailand / Q000453:epidemiology; D055815:Young Adult
C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins; D003402:Creatine Kinase