Identify mutation in amyotrophic lateral sclerosis cases using HaloPlex target enrichment system

Zhi-Jun Liu; Hong-Fu Li; Guo-He Tan; Qing-Qing Tao; Wang Ni; Xue-Wen Cheng; Zhi-Qi Xiong; Zhi-Ying Wu

doi:10.1016/j.neurobiolaging.2014.07.003

Identify mutation in amyotrophic lateral sclerosis cases using HaloPlex target enrichment system

Neurobiol Aging. 2014 Dec;35(12):2881.e11-2881.e15. doi: 10.1016/j.neurobiolaging.2014.07.003. Epub 2014 Jul 11.

Authors

Zhi-Jun Liu¹, Hong-Fu Li², Guo-He Tan³, Qing-Qing Tao¹, Wang Ni², Xue-Wen Cheng³, Zhi-Qi Xiong³, Zhi-Ying Wu⁴

Affiliations

¹ Department of Neurology and Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai, China.
² Department of Neurology and Institute of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
³ Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
⁴ Department of Neurology and Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai, China; Department of Neurology and Institute of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address: zhiyingwu@fudan.edu.cn.

PMID: 25109764
DOI: 10.1016/j.neurobiolaging.2014.07.003

Abstract

To date, at least 18 causative genes have been identified in amyotrophic lateral sclerosis (ALS). Because of the clinical and genetic heterogeneity, molecular diagnosis for ALS faces great challenges. HaloPlex target enrichment system is a new targeted sequencing approach, which can detect already known mutations or candidate genes. We performed this approach to screen 18 causative genes of ALS, including SOD1, SETX, FUS, ANG, TARDBP, ALS2, FIG4, VAPB, OPTN, DAO, VCP, UBQLN2, SPG11, SIGMAR1, DCTN1, SQSTM1, PFN1, and CHMP2B in 8 ALS probands. Using this approach, we got an average of 9.5 synonymous or missense mutations per sample. After validation by Sanger sequencing, we identified 3 documented SOD1 mutations (p.F21C, p.G148D, and p.C147R) and 1 novel DCTN1 p.G59R mutation in 4 probands. The novel DCTN1 mutation appeared to segregate with the disease in the pedigree and was absent in 200 control subjects. The high throughput and efficiency of this approach indicated that it could be applied to diagnose ALS and other inherited diseases with multiple causative genes in clinical practice.

Keywords: Amyotrophic lateral sclerosis; DCTN1; HaloPlex target enrichment system; SOD1.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Amyotrophic Lateral Sclerosis / genetics*
Dynactin Complex
Female
Genetic Association Studies / methods*
Genetic Predisposition to Disease / genetics*
Genetic Testing / methods*
High-Throughput Nucleotide Sequencing / methods*
Humans
Male
Microtubule-Associated Proteins / genetics*
Middle Aged
Mutation, Missense*
Pedigree
Superoxide Dismutase / genetics*
Superoxide Dismutase-1
Young Adult

Substances

DCTN1 protein, human
Dynactin Complex
Microtubule-Associated Proteins
SOD1 protein, human
Superoxide Dismutase
Superoxide Dismutase-1

Supplementary concepts

Amyotrophic Lateral Sclerosis 8