title: Novel mutations in ALOX12B in patients with autosomal recessive congenital ichthyosis and evidence for genetic heterogeneity on chromosome 17p13.
abstract: We report clinical and molecular findings in 20 patients from 11 families with autosomal recessive congenital ichthyosis (ARCI) linked to chromosome 17p13, and attributed to mutations in the ALOX gene cluster, which includes three lipoxygenase genes, ALOXE3, ALOX12B, and ALOX15B. We identified six novel missense mutations and one novel deletion leading to a premature stop codon in ALOX12B in only six out of the 11 families which led us to investigate a possible implication of ALOX15B. Mutation analysis of this gene, as well as ALOXE3, which is known to be mutated in some cases of ARCI, failed to reveal causative mutations in the five remaining ARCI families, indicating that other genes on chromosome 17p13 may be involved in this disease. However, by adding new variants to the repertoire of ALOX12B mutations in non-bullous congenital ichthyosiform erythroderma, our data contribute to an enlargement of the spectrum of mutations for the development of efficient molecular genetic tests for analysis of at risk individuals whose carrier status is unknown.
authors.affiliation: Centre National de Génotypage, Dermatologic Disease Projects, Evry, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Lesueur
authors.forename: Bakar
authors.initials: B
authors.lastname: Bouadjar
authors.forename: Caroline
authors.initials: C
authors.lastname: Lefèvre
authors.forename: Florence
authors.initials: F
authors.lastname: Jobard
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Audebert
authors.forename: Hakima
authors.initials: H
authors.lastname: Lakhdar
authors.forename: Ludovic
authors.initials: L
authors.lastname: Martin
authors.forename: Gianluca
authors.initials: G
authors.lastname: Tadini
authors.forename: Aysen
authors.initials: A
authors.lastname: Karaduman
authors.forename: Serap
authors.initials: S
authors.lastname: Emre
authors.forename: Safa
authors.initials: S
authors.lastname: Saker
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
authors.forename: Judith
authors.initials: J
authors.lastname: Fischer
mesh_terms: D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17; D018388:Codon, Terminator; D005260:Female; D017353:Gene Deletion; D005808:Genes, Recessive; D018740:Genetic Heterogeneity; D006801:Humans; D007057:Ichthyosis / Q000235:genetics*; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree
chemical_list: D018388:Codon, Terminator; C514086:ALOX12B protein, human; D001092:Arachidonate 12-Lipoxygenase