title: Molecular analysis of Cypriot patients with Glutaric aciduria type I: identification of two novel mutations.
abstract: OBJECTIVE
  The purpose of this study was to identify the mutations in the glutaryl-CoA dehydrogenase gene (GCDH) in ten Cypriot patients with Glutaric aciduria type I (GAI).
  
  
  METHODS
  Molecular analysis of the GCDH gene was performed by direct sequencing of the patients' genomic DNA. In silico tools were applied to predict the effect of the novel variants on the structure and function of the protein.
  
  
  RESULTS
  All disease alleles were characterized (mutation detection rate 100%). Five missense mutations were identified: c.192G>T (p.Glu64Asp) and c.803G>T (p.Gly268Val), which are novel, and three previously described mutations, c.1123T>C (p.Cys375Arg), c.1204C>T (p.Arg402Trp) and c.1286C>T (p.Thr429Met).
  
  
  CONCLUSIONS
  Two novel mutations, p.Glu64Asp and p.Gly268Val, account for the majority of disease alleles (76.5%) in Cypriot patients with Glutaric aciduria type I. A founder effect for the p.Glu64Asp and the p.Gly268Val can be suggested based on the place of origin of the carriers of these mutations. Identification of the causative mutations of GAI in Cypriot patients will facilitate carrier detection as well as post- and pre-natal diagnosis.
authors: Department of Biochemical Genetics, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors: Theodoros
authors: T
authors: Georgiou
authors: Cyprus Paediatric Neurology Institute, Nicosia, Cyprus.
authors: Paola
authors: P
authors: Nicolaidou
authors: Archbishop Makarios III Hospital, Nicosia, Cyprus.
authors: Anastasia
authors: A
authors: Hadjichristou
authors: Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors: Rodothea
authors: R
authors: Ioannou
authors: Department of Biochemical Genetics, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors: Maria
authors: M
authors: Dionysiou
authors: Archbishop Makarios III Hospital, Nicosia, Cyprus.
authors: Elli
authors: E
authors: Siama
authors: Archbishop Makarios III Hospital, Nicosia, Cyprus.
authors: Georgia
authors: G
authors: Chappa
authors: Archbishop Makarios III Hospital, Nicosia, Cyprus.
authors: Violetta
authors: V
authors: Anastasiadou
authors: Department of Biochemical Genetics, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus. Electronic address: anthidr@cing.ac.cy.
authors: Anthi
authors: A
authors: Drousiotou
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics*; D001928:Brain Diseases, Metabolic / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006580:Genetic Carrier Screening; D050770:Glutaryl-CoA Dehydrogenase / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D055815:Young Adult
chemical_list: D050770:Glutaryl-CoA Dehydrogenase
keywords: Cyprus; GCDH; Glutaric aciduria type I; Glutaryl-CoA dehydrogenase; Mutations