title: Founder effect confirmation of c.241A>G mutation in the L2HGDH gene and characterization of oxidative stress parameters in six Tunisian families with L-2-hydroxyglutaric aciduria.
abstract: L-2-hydroxyglutaric aciduria (L2HGA) is an autosomal recessive neurometabolic disorder characterized essentially by the presence of elevated levels of L-2-hydroxyglutaric acid (LGA) in plasma, cerebrospinal fluid and urine. L2HGA is caused by a deficiency in the L2-Hydroxyglutaric dehydrogenase (L2HGDH) enzyme involved in the oxidation of LGA to the alpha 2-ketoglutarate. LGA has been proposed as an endo- and exogenous cytotoxic organic acid that induces free radical formation and generation of reactive oxygen species (ROS). In this report, we analyzed 14 L2HGA patients belonging to six unrelated consanguineous families the south of Tunisia. The patients were diagnosed with L2HGA disease confirmed on the presence of high level of LGA in urine. We analyzed the L2HGDH gene in all probands and identified the same c.241A>G homozygous mutation, which was previously reported in Tunisia. We also used intragenic single nucleotide length polymorphisms (SNPs) and two extragenic microsatellites flanking the L2HGDH gene to confirm the founder effect of c.241A>G mutation in the 14 studied cases. In addition, we carried out the measurement of the oxidative stress parameters in the plasma of L2HGA patients which revealed a significant increase in the malondialdehyde levels (MDA), a biomarker of lipid peroxydation, and the reduced glutathione (GSH). A diminution of the antioxidant enzyme activities including superoxide dismutase (SOD), glutathione peroxidase (GPx), was also observed.
authors.affiliation: Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax, Sfax, Tunisia.
authors.forename: Nadege Kammoun
authors.initials: NK
authors.lastname: Jellouli
authors.affiliation: Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax, Sfax, Tunisia.
authors.forename: Ikhlass
authors.initials: I
authors.lastname: Hadj Salem
authors.affiliation: Service de Neurologie Pédiatrique, C.H.U Hédi Chaker de Sfax, Sfax, Tunisia.
authors.forename: Emna
authors.initials: E
authors.lastname: Ellouz
authors.affiliation: Laboratoire de Physiologie Animale, Departments des science de la vie, Faculté des Sciences de Sfax, Université de Sfax, Sfax, Tunisia.
authors.forename: Zeineb
authors.initials: Z
authors.lastname: Kamoun
authors.affiliation: Service de Neurologie Pédiatrique, C.H.U Hédi Chaker de Sfax, Sfax, Tunisia.
authors.forename: Fatma
authors.initials: F
authors.lastname: kamoun
authors.affiliation: Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax, Sfax, Tunisia.
authors.forename: Abdelaziz
authors.initials: A
authors.lastname: tlili
authors.affiliation: unité de recherche 05/UR/08-08, département de biochimie, hopital Rabta, Tunis, Tunisie.
authors.forename: Naziha
authors.initials: N
authors.lastname: Kaabachi
authors.affiliation: Service de Neurologie Pédiatrique, C.H.U Hédi Chaker de Sfax, Sfax, Tunisia.
authors.forename: Chanez
authors.initials: C
authors.lastname: Triki
authors.affiliation: Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax, Sfax, Tunisia.
authors.forename: Faiza
authors.initials: F
authors.lastname: Fakhfakh
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D020739:Brain Diseases, Metabolic, Inborn / Q000235:genetics* / Q000378:metabolism; D005260:Female; D018703:Founder Effect; D005978:Glutathione / Q000097:blood; D006801:Humans; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D018895:Microsatellite Repeats; D009154:Mutation; D018384:Oxidative Stress / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D014416:Tunisia
chemical_list: D008315:Malondialdehyde; D000429:Alcohol Oxidoreductases; C506763:L2HGDH protein, human; D005978:Glutathione