title: New disease allele and de novo mutation indicate mutational vulnerability of titin exon 343 in hereditary myopathy with early respiratory failure.
abstract: We report two patients of Chinese ancestry with hereditary myopathy with early respiratory failure, one sporadic with atypical onset as rigid spine syndrome, the other familial with 10 years' history of hyperCKemia. Muscle biopsy was either nonspecific or typical with cytoplasmic bodies and rimmed vacuoles. Despite the phenotypic variety, both patients showed fatty infiltration of semitendinosus on muscle magnetic resonance imaging. Genetic analysis of case 1 disclosed de novo heterozygous missense mutations in the 119th fibronectin 3 domain of titin [c.90272C>T, p.P30091L]. Haplotype analysis of case 2 revealed a heterozygous missense mutation [c.90211T>C, p.C30071R] on a new disease allele incompatible with the British common haplotype. These findings suggest that hereditary myopathy with early respiratory failure is a worldwide distributed disorder and indicate the mutational vulnerability of TTN exon 343 in which de novo mutations could occur on different haplotype backgrounds.
authors.affiliation: Department of Neurology, Huashan Hospital, Fudan University, China.
authors.forename: Dongyue
authors.initials: D
authors.lastname: Yue
authors.affiliation: Department of Neuropathology, Huashan Hospital, Fudan University, China.
authors.forename: Mingshi
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Neurology, Huashan Hospital, Fudan University, China. Electronic address: whzhu@fudan.edu.cn.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Huashan Hospital, Fudan University, China.
authors.forename: Sushan
authors.initials: S
authors.lastname: Luo
authors.affiliation: Department of Neurology, Huashan Hospital, Fudan University, China.
authors.forename: Jianying
authors.initials: J
authors.lastname: Xi
authors.affiliation: Department of Neurology, Jing'an District Center Hospital of Shanghai, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Neurology, Jing'an District Center Hospital of Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurology, Huashan Hospital, Fudan University, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Cai
authors.affiliation: Department of Radiology, Jing'an District Center Hospital of Shanghai, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neuropathology, Huashan Hospital, Fudan University, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurology, Huashan Hospital, Fudan University, China.
authors.forename: Jiahong
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Neurology, Jing'an District Center Hospital of Shanghai, China. Electronic address: zhao_chongbo@fudan.edu.cn.
authors.forename: Chongbo
authors.initials: C
authors.lastname: Zhao
mesh_terms: D000328:Adult; D064211:Connectin / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics*; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D006801:Humans; D008297:Male; D009135:Muscular Diseases / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D012131:Respiratory Insufficiency / Q000235:genetics*; D055815:Young Adult
chemical_list: D064211:Connectin; C577285:TTN protein, human
keywords: Cytoplasmic body; Haplotype; Hereditary myopathy with early respiratory failure; Muscle magnetic resonance imaging; Rigid spine syndrome; TTN gene