Mutation screening of SLC52A3, C19orf12, and TARDBP in Iranian ALS patients

Neurobiol Aging. 2019 Mar:75:225.e9-225.e14. doi: 10.1016/j.neurobiolaging.2018.11.003. Epub 2018 Nov 16.

Abstract

Mutations in the same gene are sometimes the cause of different clinically diagnosed neurologic disorders; this emphasizes interrelationships between various neurologic diseases. In this light, we screened SLC52A3, which is the cause of Brown-Vialetto-Van Laere syndrome, and C19orf12, which is the cause of neurodegeneration with brain iron accumulation in 60 Iranian amyotrophic lateral sclerosis (ALS) patients without mutations in the 2 most important ALS-causing genes, SOD1 and C9orf72. To the best of our knowledge, neither SLC52A3 nor C19orf12 has been mutation-screened previously in ALS cohorts. Justification for screening SLC52A3 included notable clinical similarities between Brown-Vialetto-Van Laere syndrome and ALS, and justification for screening C19orf12 was known contribution of mitochondrial dysfunction to ALS etiology. Disease-causing variations in the 2 genes were not found among the ALS patients. TARDBP was screened in 107 patients, and a mutation (p.Gly348Cys) was identified in one. Detailed clinical data on the patient are presented. It appears that mutations in TARDBP in ALS patients of Iran are rare and occur at similar frequencies to European populations.

Keywords: ALS; C19orf12; Iran; SLC52A3; TARDBP; p.Gly348Cys.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amyotrophic Lateral Sclerosis / genetics*
  • Bulbar Palsy, Progressive / genetics*
  • DNA-Binding Proteins / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Hearing Loss, Sensorineural / genetics*
  • Humans
  • Iran
  • Male
  • Membrane Transport Proteins / genetics*
  • Middle Aged
  • Mitochondrial Proteins / genetics*
  • Mutation / genetics
  • Superoxide Dismutase-1 / genetics

Substances

  • C19orf12 protein, human
  • DNA-Binding Proteins
  • Membrane Transport Proteins
  • Mitochondrial Proteins
  • SLC52A3 protein, human
  • TARDBP protein, human
  • Superoxide Dismutase-1

Supplementary concepts

  • Brown-Vialetto-Van Laere syndrome