Targeted Next-Generation Sequencing Revealed Novel Mutations in Chinese Ataxia Telangiectasia Patients: A Precision Medicine Perspective

Zhao Chen; Wei Ye; Zhe Long; Dongxue Ding; Huirong Peng; Xuan Hou; Rong Qiu; Kun Xia; Beisha Tang; Hong Jiang

doi:10.1371/journal.pone.0139738

Targeted Next-Generation Sequencing Revealed Novel Mutations in Chinese Ataxia Telangiectasia Patients: A Precision Medicine Perspective

PLoS One. 2015 Oct 6;10(10):e0139738. doi: 10.1371/journal.pone.0139738. eCollection 2015.

Authors

Zhao Chen¹, Wei Ye¹, Zhe Long¹, Dongxue Ding¹, Huirong Peng¹, Xuan Hou¹, Rong Qiu², Kun Xia³, Beisha Tang⁴, Hong Jiang⁴

Affiliations

¹ Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
² School of Information Science and Engineering, Central South University, Changsha, Hunan, P.R. China.
³ State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, P.R. China.
⁴ 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.

Abstract

Ataxia telangiectasia (AT) is an autosomal recessive disease characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia and immunodeficiency due to mutations in the ATM gene. We performed targeted next-generation sequencing (NGS) on three unrelated patients and identified five disease-causing variants in three probands, including two pairs of heterozygous variants (FAT-1:c.4396C>T/p.R1466X, c.1608-2A>G; FAT-2:c.4412_4413insT/p.L1472Ffs*19, c.8824C>T/p.Q2942X) and one pair of homozygous variants (FAT-3: c.8110T>G/p.C2704G, Hom). With regard to precision medicine for rare genetic diseases, targeted NGS currently enables the rapid and cost-effective identification of causative mutations and is an updated molecular diagnostic tool that merits further optimization. This high-throughput data-based strategy would propel the development of precision diagnostic methods and establish a foundation for precision medicine.

Publication types

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

MeSH terms

Ataxia Telangiectasia / diagnosis*
Ataxia Telangiectasia / genetics*
Ataxia Telangiectasia Mutated Proteins / genetics*
Child
China
Female
Genes, Recessive
High-Throughput Nucleotide Sequencing
Humans
Male
Mutation*
Precision Medicine

Substances

ATM protein, human
Ataxia Telangiectasia Mutated Proteins

Grants and funding

This study was supported by the National Basic Research Program (973 Program) (Nos. 2012CB944601, 2012CB517902 and 2011CB510002 to Hong Jiang), the National Natural Science Foundation of China (Nos. 81410308019, 81471156, 81271260, and 30971585 to Hong Jiang; No. 31401135 to Rong Qiu), Hunan Funds for Distinguished Young Scientists (No. 14JJ1008 to Hong Jiang), Xinjiang Natural Science Foundation (No. 201318101-4 to Hong Jiang), the Undergraduate Innovation Project of Central South University (Nos. YB13028 and 201410533324 to Hong Jiang), Fundamental Research Funds for the Central Universities of Central South University (No. 2014zzts078 to Zhao Chen), and High-level medical personnel of Hunan province “225” Project. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.