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Mutation spectrum of Chinese patients with familial and sporadic amyotrophic lateral sclerosis
  1. Qing Liu1,2,
  2. Fang Liu2,3,
  3. Bo Cui1,2,
  4. Chao Xia Lu2,3,
  5. Xia Nan Guo2,3,
  6. Rong Rong Wang2,3,
  7. Ming Sheng Liu1,2,
  8. Xiao Guang Li1,2,
  9. Li-ying Cui1,2,
  10. Xue Zhang1,2,3
  1. 1 Department of Neurology and Laboratory of Clinical Genetics, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing, China
  2. 2 Neuroscience Center, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS), Beijing, China
  3. 3 McKusick-Zhang Center for Genetic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
  1. Correspondence to Professor Xue Zhang, McKusick-Zhang Center for Genetic Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China; xuezhang{at}pumc.edu.cnProfessor Li-ying Cui, Department of Neurology and Laboratory of Clinical Genetics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China; pumchcuily{at}sina.comQL and FL contributed equally.

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Introduction

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterised by motor neuron degeneration in the primary motor cortex, brainstem and spinal cord. In two studies, >20 genes were associated with ALS and a number of patients carried potentially pathogenic variants in multiple ALS genes.1 ,2 We investigated the burden of influence of variants on ALS phenotype, and genetic profile of familial ALS (FALS) and sporadic ALS (SALS) in Chinese patients.

Methods

From 2009 to 2014, 254 Chinese patients diagnosed as having probable or definite ALS according to El Escorial criteria,3 at our clinic centre, were enrolled for genetic study. FALS was defined as patients having a first-degree relative with ALS. Multiple neurodegenerative genes including 24 known ALS genes (SOD1, ALS2, SETX, FUS, VAPB, ANG, TARDBP, FIG4, OPTN, VCP, UBQLN2, SIGMAR1, CHMP2B, PFN1, C9ORF72, ATXN2, AR, DCTN1, NEFH, PRPH, DAO, TFG, TAF15 and GRN) were incorporated into one screening panel, for sequence analysis. Detailed methods for targeting next-generation sequencing can be seen in online supplementary materials. In short, genomic DNA was extracted from peripheral blood leucocytes, and selective Ion Sphere Particles (ISPs) with qualified DNA were sequenced on Ion 318 Chips (8 samples/chip) by Ion Personal Genome Machine (PGM) Sequencer. At least 300 000 reads with a quality score of were obtained per sample, with a coverage of ∼96.5% for targeted regions …

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