title: Mutation in the caveolin-3 gene causes asymmetrical distal myopathy.
abstract: Mutations in the gene encoding caveolin-3 (CAV3) can cause a broad spectrum of clinical phenotypes, including limb girdle muscular dystrophy, rippling muscle disease, distal myopathy (MD), idiopathic persistent elevation of serum creatine kinase and cardiomyopathy. MD is a relatively rare subtype of caveolinopathy. Here, we report a sporadic case of a middle-aged female Chinese patient with MD in which a CAV3 mutation was identical to that previously reported in cases of rippling muscle disease. T1-weighted enhanced skeletal muscle MRI of the lower limbs showed an abnormal signal in the distal and proximal muscles. A muscle biopsy revealed moderate dystrophic changes, and immunohistochemical staining showed reduced CAV-3 expression in the plasmalemma. Genetic analysis revealed a heterozygous c.136G > A (p.Ala46Thr) CAV3 mutation that appeared to be de novo because it was absent from the patient's parents. This study suggested that the CAV3 c.136G > A (p.Ala46Thr) mutation can cause MD as well as different phenotypes in different individuals, suggesting that additional unknown loci must affect the disease phenotypes.
authors.affiliation: Department of Neurology, Peking University Shenzhen Hospital, Shenzhen, China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Neurology, Peking University Shenzhen Hospital, Shenzhen, China.
authors.forename: Wenshuang
authors.initials: W
authors.lastname: Zeng
authors.affiliation: Department of Neurology, Peking University Shenzhen Hospital, Shenzhen, China.
authors.forename: Chunxi
authors.initials: C
authors.lastname: Han
authors.affiliation: Department of Neurology, Peking University Shenzhen Hospital, Shenzhen, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Neurology, Peking University Shenzhen Hospital, Shenzhen, China.
authors.forename: Haiou
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Peking University Shenzhen Hospital, Shenzhen, China.
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Tong
mesh_terms: D000328:Adult; D044466:Asian People; D051244:Caveolin 3 / Q000235:genetics*; D049310:Distal Myopathies / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006579:Heterozygote; D006801:Humans; D035002:Lower Extremity / Q000000981:diagnostic imaging / Q000473:pathology; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging / Q000473:pathology; D009154:Mutation; D010375:Pedigree; D010641:Phenotype
chemical_list: C417736:CAV3 protein, human; D051244:Caveolin 3
keywords: caveolin-3; caveolinopathy; de novo mutation; distal myopathy; next generation sequencing