title: Using next-generation sequencing as a genetic diagnostic tool in rare autosomal recessive neurologic Mendelian disorders.
abstract: Next-generation sequencing was used to investigate 9 rare Chinese pedigrees with rare autosomal recessive neurologic Mendelian disorders. Five probands with ataxia-telangectasia and 1 proband with chorea-acanthocytosis were analyzed by targeted gene sequencing. Whole-exome sequencing was used to investigate 3 affected individuals with Joubert syndrome, nemaline myopathy, or spastic ataxia Charlevoix-Saguenay type. A list of known and novel candidate variants was identified for each causative gene. All variants were genetically verified by Sanger sequencing or quantitative polymerase chain reaction with the strategy of disease segregation in related pedigrees and healthy controls. The advantages of using next-generation sequencing to diagnose rare autosomal recessive neurologic Mendelian disorders characterized by genetic and phenotypic heterogeneity are demonstrated. A genetic diagnostic strategy combining the use of targeted gene sequencing and whole-exome sequencing with the aid of next-generation sequencing platforms has shown great promise for improving the diagnosis of neurologic Mendelian disorders.
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, PR China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Chen
authors.forename: Jun-Ling
authors.initials: JL
authors.lastname: Wang
authors.forename: Bei-Sha
authors.initials: BS
authors.lastname: Tang
authors.forename: Zhan-Fang
authors.initials: ZF
authors.lastname: Sun
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Shi
authors.forename: Lu
authors.initials: L
authors.lastname: Shen
authors.forename: Li-Fang
authors.initials: LF
authors.lastname: Lei
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Wei
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Xiao
authors.forename: Zheng-Mao
authors.initials: ZM
authors.lastname: Hu
authors.forename: Qian
authors.initials: Q
authors.lastname: Pan
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
authors.forename: Qing-Yan
authors.initials: QY
authors.lastname: Zhang
authors.forename: Mei-Zhi
authors.initials: MZ
authors.lastname: Dai
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ashizawa
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000015:Abnormalities, Multiple; D000328:Adult; D044466:Asian People / Q000235:genetics; D001259:Ataxia; D001483:Base Sequence / Q000235:genetics*; D001921:Brain / Q000473:pathology; D002526:Cerebellar Diseases; D002531:Cerebellum / Q000002:abnormalities; D002648:Child; D002675:Child, Preschool; D059472:Exome / Q000235:genetics*; D005124:Eye Abnormalities; D005260:Female; D005808:Genes, Recessive / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008607:Intellectual Disability; D052177:Kidney Diseases, Cystic; D008279:Magnetic Resonance Imaging; D008297:Male; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D009128:Muscle Spasticity; D017696:Myopathies, Nemaline; D009422:Nervous System Diseases / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D054546:Neuroacanthocytosis; D009896:Optic Atrophy; D012160:Retina / Q000002:abnormalities; D017422:Sequence Analysis, DNA / Q000379:methods*; D020754:Spinocerebellar Ataxias; D013684:Telangiectasis; D055815:Young Adult
keywords: Autosomal recessive; Exome sequencing; Genetic diagnostic strategy; Neurologic Mendelian disorders; Targeted gene sequencing