The distinct genetic pattern of ALS in Turkey and novel mutations

Neurobiol Aging. 2015 Apr;36(4):1764.e9-1764.e18. doi: 10.1016/j.neurobiolaging.2014.12.032. Epub 2015 Jan 10.

Abstract

The frequency of amyotrophic lateral sclerosis (ALS) mutations has been extensively investigated in several populations; however, a systematic analysis in Turkish cases has not been reported so far. In this study, we screened 477 ALS patients for mutations, including 116 familial ALS patients from 82 families and 361 sporadic ALS (sALS) cases. Patients were genotyped for C9orf72 (18.3%), SOD1 (12.2%), FUS (5%), TARDBP (3.7%), and UBQLN2 (2.4%) gene mutations, which together account for approximately 40% of familial ALS in Turkey. No SOD1 mutations were detected in sALS patients; however, C9orf72 (3.1%) and UBQLN2 (0.6%) explained 3.7% of sALS in the population. Exome sequencing revealed mutations in OPTN, SPG11, DJ1, PLEKHG5, SYNE1, TRPM7, and SQSTM1 genes, many of them novel. The spectrum of mutations reflect both the distinct genetic background and the heterogeneous nature of the Turkish ALS population.

Keywords: ALS; C9orf72; FUS; SOD1; TDP-43; Turkey.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adolescent
  • Adult
  • Aged
  • Amyotrophic Lateral Sclerosis / genetics*
  • Autophagy-Related Proteins
  • C9orf72 Protein
  • Cell Cycle Proteins / genetics
  • Cytoskeletal Proteins
  • DNA-Binding Proteins / genetics
  • Exome / genetics
  • Female
  • Genetic Association Studies*
  • Guanine Nucleotide Exchange Factors / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Male
  • Membrane Transport Proteins
  • Middle Aged
  • Mutation / genetics*
  • Nerve Tissue Proteins / genetics
  • Nuclear Proteins / genetics
  • Oncogene Proteins / genetics
  • Protein Deglycase DJ-1
  • Protein Serine-Threonine Kinases / genetics
  • Proteins / genetics*
  • RNA-Binding Protein FUS / genetics*
  • Sequestosome-1 Protein
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase-1
  • TRPM Cation Channels / genetics
  • Transcription Factor TFIIIA / genetics
  • Turkey
  • Ubiquitins / genetics
  • Young Adult

Substances

  • Adaptor Proteins, Signal Transducing
  • Autophagy-Related Proteins
  • C9orf72 Protein
  • C9orf72 protein, human
  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • FUS protein, human
  • Guanine Nucleotide Exchange Factors
  • Intracellular Signaling Peptides and Proteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • OPTN protein, human
  • Oncogene Proteins
  • PLEKHG5 protein, human
  • Proteins
  • RNA-Binding Protein FUS
  • SOD1 protein, human
  • SPG11 protein, human
  • SQSTM1 protein, human
  • SYNE1 protein, human
  • Sequestosome-1 Protein
  • TARDBP protein, human
  • TRPM Cation Channels
  • Transcription Factor TFIIIA
  • UBQLN2 protein, human
  • Ubiquitins
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • Protein Serine-Threonine Kinases
  • TRPM7 protein, human
  • PARK7 protein, human
  • Protein Deglycase DJ-1