title: Identification of a de novo DYNC1H1 mutation via WES according to published guidelines.
abstract: De novo mutations that contribute to rare Mendelian diseases, including neurological disorders, have been recently identified. Whole-exome sequencing (WES) has become a powerful tool for the identification of inherited and de novo mutations in Mendelian diseases. Two important guidelines were recently published regarding the investigation of causality of sequence variant in human disease and the interpretation of novel variants identified in human genome sequences. In this study, a family with supposed movement disorders was sequenced via WES (including the proband and her unaffected parents), and a standard investigation and interpretation of the identified variants was performed according to the published guidelines. We identified a novel de novo mutation (c.2327C > T, p.P776L) in DYNC1H1 gene and confirmed that it was the causal variant. The phenotype of the affected twins included delayed motor milestones, pes cavus, lower limb weakness and atrophy, and a waddling gait. Electromyographic (EMG) recordings revealed typical signs of chronic denervation. Our study demonstrates the power of WES to discover the de novo mutations associated with a neurological disease on the whole exome scale, and guidelines to conduct WES studies and interpret of identified variants are a preferable option for the exploration of the pathogenesis of rare neurological disorders.
authors: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
authors: Dongxue
authors: D
authors: Ding
authors: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
authors: Zhao
authors: Z
authors: Chen
authors: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
authors: Kai
authors: K
authors: Li
authors: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
authors: Zhe
authors: Z
authors: Long
authors: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
authors: Wei
authors: W
authors: Ye
authors: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
authors: Zhaoli
authors: Z
authors: Tang
authors: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, P.R. China.
authors: Kun
authors: K
authors: Xia
authors: School of Information Science and Engineering, Central South University, Changsha, China.
authors: Rong
authors: R
authors: Qiu
authors: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.|Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, P.R. China.|State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, P.R. China.
authors: Beisha
authors: B
authors: Tang
authors: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.|Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, P.R. China.|State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, P.R. China.
authors: Hong
authors: H
authors: Jiang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D056445:Cytoplasmic Dyneins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004576:Electromyography; D059472:Exome; D005260:Female; D005530:Foot Deformities / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D015894:Genome, Human; D006801:Humans; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014427:Twins; D055815:Young Adult
chemical_list: C511240:DYNC1H1 protein, human; D056445:Cytoplasmic Dyneins