title: Molecular determination of glutaric aciduria type I in individuals from southwest Iran.
abstract: BACKGROUND
  Glutaric Aciduria type 1 (GA1) is a metabolic inborn error and is characterized by increasing excursion of glutaric acid and its derivates, presented in microcephaly and dystonia. The disease is resulted from mutational inactivation in the GCDH gene encoding the glutaryl-CoA dehydrogenase. The defective enzyme causes the accumulation of an excessive level of intermediate breakdown products that leads to the brain damage. In spite of the clinical features, diagnosis of GAI has been often confusing, because of variability in the clinical manifestations of patients. Early diagnosis and treatment can though prevent irreversible disease progression and consequent brain damage; otherwise the affected individuals will die in their first decade of lives.
  
  
  METHODS
  The GCDH gene was also analyzed to (detect or identify) disease causing mutations using gene amplification and direct sequencing in 18 patients.
  
  
  RESULTS
  Among 18 patients, 10 patients (55.5%) were homozygous or compounded heterozygous for the recurrent mutation E181Q, three patients (16.7%) were homozygous for the known mutation R402Q and one patient (5.6%) was compound heterozygous for S255L. All three detected missense mutations are pathogenic, which cause structural changes in the binding site and tetramerization or functional deficiency. Four other individuals (22.2%) with a preliminary diagnosis of GAI were negative for any pathogenic mutations.
  
  
  CONCLUSIONS
  Most GA1 affected persons in southwest Iran are with Persian ethnicity and the most common mutation in Khuzestan Province is prominent in comparison to  previous reports from Iran.
authors.affiliation: Toxicology Research Center, Ahvaz Medical School of Jundishapur University, Ahvaz, Iran. galehdari187@yahoo.com.
authors.forename: Masumeh
authors.initials: M
authors.lastname: Baradaran
authors.affiliation: Department of Genetics, Shahid Chamran University, Ahvaz, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Galehdari
authors.affiliation: Ahvaz Medical School of Jundishapur University, Ahvaz, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Aminzadeh
authors.affiliation: Ahvaz Medical School of Jundishapur University, Ahvaz, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Azizi Malmiri
authors.affiliation: Toxicology Research Center, Ahvaz Medical School of Jundishapur University, Ahvaz, Iran.
authors.forename: Raheleh
authors.initials: R
authors.lastname: Tangestani
authors.affiliation: Department of Genetics, Shahid Chamran University, Ahvaz, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Karimi
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D001928:Brain Diseases, Metabolic / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D020134:Catalytic Domain; D050770:Glutaryl-CoA Dehydrogenase / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007492:Iran / Q000453:epidemiology; D020125:Mutation, Missense / Q000235:genetics; D017433:Protein Structure, Secondary
chemical_list: D050770:Glutaryl-CoA Dehydrogenase