title: Exome sequencing identifies a novel TTN mutation in a family with hereditary myopathy with early respiratory failure.
abstract: Myofibrillar myopathy (MFM) is a group of chronic muscular disorders that show the focal dissolution of myofibrils and accumulation of degradation products. The major genetic basis of MFMs is unknown. In 1993, our group reported a Japanese family with dominantly inherited cytoplasmic body myopathy, which is now included in MFM, characterized by late-onset chronic progressive distal muscle weakness and early respiratory failure. In this study, we performed linkage analysis and exome sequencing on these patients and identified a novel c.90263G>T mutation in the TTN gene (NM_001256850). During the course of our study, another groups reported three mutations in TTN in patients with hereditary myopathy with early respiratory failure (HMERF, MIM #603689), which is characterized by overlapping pathologic findings with MFMs. Our patients were clinically compatible with HMERF. The mutation identified in this study and the three mutations in patients with HMERF were located on the A-band domain of titin, suggesting a strong relationship between mutations in the A-band domain of titin and HMERF. Mutation screening of TTN has been rarely carried out because of its huge size, consisting of 363 exons. It is possible that focused analysis of TTN may detect more mutations in patients with MFMs, especially in those with early respiratory failure.
authors: Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan.
authors: Rumiko
authors: R
authors: Izumi
authors: Tetsuya
authors: T
authors: Niihori
authors: Yoko
authors: Y
authors: Aoki
authors: Naoki
authors: N
authors: Suzuki
authors: Masaaki
authors: M
authors: Kato
authors: Hitoshi
authors: H
authors: Warita
authors: Toshiaki
authors: T
authors: Takahashi
authors: Maki
authors: M
authors: Tateyama
authors: Takeshi
authors: T
authors: Nagashima
authors: Ryo
authors: R
authors: Funayama
authors: Koji
authors: K
authors: Abe
authors: Keiko
authors: K
authors: Nakayama
authors: Masashi
authors: M
authors: Aoki
authors: Yoichi
authors: Y
authors: Matsubara
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D001706:Biopsy; D064211:Connectin / Q000235:genetics*; D059472:Exome; D005260:Female; D005787:Gene Frequency; D030342:Genetic Diseases, Inborn / Q000175:diagnosis / Q000235:genetics*; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009135:Muscular Diseases / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D012131:Respiratory Insufficiency / Q000175:diagnosis / Q000235:genetics*; D014057:Tomography, X-Ray Computed
chemical_list: D064211:Connectin; C577285:TTN protein, human