title: Pyridoxine-dependent epilepsy in Tunisia is caused by a founder missense mutation of the ALDH7A1 gene.
abstract: Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive disorder characterized by seizures and therapeutic response to pharmacological dose of pyridoxine. Mutations in the ALDH7A1 gene, encoding α-aminoadipic semialdehyde (α-AASA) dehydrogenase (antiquitin), have been reported to cause PDE in most patients. In this study molecular analysis of seven PDE Tunisian patients revealed a common missense c.1364T>C mutation in the ALDH7A1 gene. The identification of a cluster of PDE pedigrees carrying the c.1364T>C mutation in a specific area raises the question of the origin of this mutation from a common ancestor. We carried out a genotype-based analysis by way of genotyping a new generated microsatellite marker within the ALDH7A1 gene. Genotype reconstruction of all affected pedigree members indicate that all c.1364T>C mutation carriers harbored the same allele, indicating a common ancestor. The finding of a founder effect in a rare disease is essential for the genetic diagnosis and the genetic counseling of affected PDE pedigrees in Tunisia.
authors: Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax, Tunisia. Abdelaziz.Tlili@fss.rnu.tn
authors: Abdelaziz
authors: A
authors: Tlili
authors: Nadia
authors: N
authors: Hamida Hentati
authors: Rim
authors: R
authors: Chaabane
authors: Abdellatif
authors: A
authors: Gargouri
authors: Faiza
authors: F
authors: Fakhfakh
mesh_terms: D000328:Adult; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D004827:Epilepsy / Q000235:genetics*; D018703:Founder Effect; D005838:Genotype; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D020125:Mutation, Missense; D011736:Pyridoxine / Q000627:therapeutic use; D014416:Tunisia
chemical_list: C089507:ALDH7A1 protein, human; D000444:Aldehyde Dehydrogenase; D011736:Pyridoxine