title: Sjögren-Larsson syndrome: novel mutations in the ALDH3A2 gene in a French cohort.
abstract: Sjogren-Larsson syndrome (SLS) is a rare autosomal recessive disorder characterized by ichthyosis, spastic di- or tetraplegia and mental retardation due a defect of the fatty aldehyde dehydrogenase (FALDH), related to mutations in the ALDH3A2 gene. In this study, we screened a French cohort of patients with Sjögren-Larsson syndrome (SLS) for mutations in the ALDH3A2 gene. The five unrelated patients with typical SLS all present mutations in this gene. Three novel mutations were identified whereas three other ones were previously described. We also realized functional analyses at the mRNA level for two splice site mutations to study their deleterious consequences. Two of the previously described mutations had already been identified in the same region of Europe, suggesting a putative founder effect. We suggest that, (1) when clinical and MR features are present, direct sequencing of the ALDH3A2 gene in SLS is of particular interest without necessity of a skin biopsy for enzymatic assay in order to propose genetic counsel and (2) identification of mutations already described in the same population with putative founder effects may simplify genetic analysis in this context.
authors.affiliation: Génétique, Reproduction et Développement, Unité Mixte de Recherche 931 (Institut National de la Santé et de la Recherche médicale), Faculté de médecine, Clermont-Ferrand, France. csarret@chu-clermontferrand.fr
authors.forename: Catherine
authors.initials: C
authors.lastname: Sarret
authors.forename: Mélanie
authors.initials: M
authors.lastname: Rigal
authors.forename: Catherine
authors.initials: C
authors.lastname: Vaurs-Barrière
authors.forename: Imen
authors.initials: I
authors.lastname: Dorboz
authors.forename: Eléonore
authors.initials: E
authors.lastname: Eymard-Pierre
authors.forename: Patricia
authors.initials: P
authors.lastname: Combes
authors.forename: Geneviève
authors.initials: G
authors.lastname: Giraud
authors.forename: Ronald J A
authors.initials: RJ
authors.lastname: Wanders
authors.forename: Alexandra
authors.initials: A
authors.lastname: Afenjar
authors.forename: Christine
authors.initials: C
authors.lastname: Francannet
authors.forename: Odile
authors.initials: O
authors.lastname: Boespflug-Tanguy
mesh_terms: D000293:Adolescent; D000445:Aldehyde Oxidoreductases / Q000235:genetics*; D002648:Child; D015331:Cohort Studies; D005260:Female; D005602:France; D006801:Humans; D007223:Infant; D008297:Male; D017354:Point Mutation / Q000235:genetics*; D011859:Radiography; D016111:Sjogren-Larsson Syndrome / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology
chemical_list: D000445:Aldehyde Oxidoreductases; C038828:long-chain-aldehyde dehydrogenase