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 us...

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Bibliographic Details
Published in:Neurobiology of aging 2013-10, Vol.34 (10), p.2442.e11-2442.e17
Main Authors: Chen, Zhao, Wang, Jun-ling, Tang, Bei-sha, Sun, Zhan-fang, Shi, Yu-ting, Shen, Lu, Lei, Li-fang, Wei, Xiao-ming, Xiao, Jing-jing, Hu, Zheng-mao, Pan, Qian, Xia, Kun, Zhang, Qing-yan, Dai, Mei-zhi, Liu, Yu, Ashizawa, Tetsuo, Jiang, Hong
Format: Article
Language:English
Subjects:
Abnormalities, Multiple
Adult
Aging
Asian Continental Ancestry Group - genetics
Ataxia
Autosomal recessive
Base Sequence - genetics
Brain - pathology
Cerebellar Diseases
Cerebellum - abnormalities
Child
Child, Preschool
Exome - genetics
Exome sequencing
Eye Abnormalities
Female
Genes, Recessive - genetics
Genetic diagnostic strategy
Humans
Infant
Infant, Newborn
Intellectual Disability
Internal Medicine
Kidney Diseases, Cystic
Magnetic Resonance Imaging
Male
Molecular Diagnostic Techniques - methods
Muscle Spasticity
Myopathies, Nemaline
Nervous System Diseases - diagnosis
Nervous System Diseases - genetics
Nervous System Diseases - pathology
Neuroacanthocytosis
Neurologic Mendelian disorders
Neurology
Optic Atrophy
Retina - abnormalities
Sequence Analysis, DNA - methods
Spinocerebellar Ataxias
Targeted gene sequencing
Telangiectasis
Young Adult
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Summary: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.
ISSN:0197-4580
1558-1497
DOI:10.1016/j.neurobiolaging.2013.04.029