title: Genetic diagnosis of two dopa-responsive dystonia families by exome sequencing.
abstract: Dopa-responsive dystonia, a rare disorder typically presenting in early childhood with lower limb dystonia and gait abnormality, responds well to levodopa. However, it is often misdiagnosed with the wide spectrum of phenotypes. By exome sequencing, we make a rapid genetic diagnosis for two atypical dopa-responsive dystonia pedigrees. One pedigree, presented with prominent parkinsonism, was misdiagnosed as Parkinson's disease until a known mutation in GCH1 (GTP cyclohydrolase 1) gene (NM_000161.2: c.631_632delAT, p.Met211ValfsX38) was found. The other pedigree was detected with a new compound heterozygous mutation in TH (tyrosine hydroxylase) gene [(NM_000360.3: c.911C>T, p.Ala304Val) and (NM_000360.3: c.1358G>A, p.Arg453His)], whose proband, a pregnant woman, required a rapid and less-biased genetic diagnosis. In conclusion, we demonstrated that exome sequencing could provide a precise and rapid genetic testing in the diagnosis of Mendelian diseases, especially for diseases with wide phenotypes.
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Zhan-fang
authors.initials: ZF
authors.lastname: Sun
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Yu-han
authors.initials: YH
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, China.
authors.forename: Ji-feng
authors.initials: JF
authors.lastname: Guo
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Qi-ying
authors.initials: QY
authors.lastname: Sun
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Jun-pu
authors.initials: JP
authors.lastname: Mei
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Han-lin
authors.initials: HL
authors.lastname: Zhou
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Li-ping
authors.initials: LP
authors.lastname: Guan
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Jin-yong
authors.initials: JY
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, China.
authors.forename: Zheng-mao
authors.initials: ZM
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, China.
authors.forename: Jia-da
authors.initials: JD
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, China.
authors.forename: Xin-xiang
authors.initials: XX
authors.lastname: Yan
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, China; State Key Laboratory of Medical Genetics, Central South University, Changsha, China.
authors.forename: Bei-sha
authors.initials: BS
authors.lastname: Tang
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D001483:Base Sequence; D002457:Cell Extracts; D002675:Child, Preschool; D020821:Dystonic Disorders / Q000175:diagnosis* / Q000235:genetics*; D059472:Exome / Q000235:genetics*; D005260:Female; D006136:GTP Cyclohydrolase / Q000737:chemistry / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods*; D014162:Transfection; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D055815:Young Adult
chemical_list: D002457:Cell Extracts; D050505:Mutant Proteins; D014446:Tyrosine 3-Monooxygenase; D006136:GTP Cyclohydrolase