title: The sound of silence: autosomal recessive congenital ichthyosis caused by a synonymous mutation in ABCA12.
abstract: Autosomal recessive congenital ichthyosis refers to a heterogeneous group of cornification disorders of major impact on patients' life. The disease has been linked so far to mutations in 8 distinct genes. We report a consanguineous family of Arab Muslim origin with several members displaying a severe form of congenital ichthyosiform erythroderma. Using a panel of polymorphic microsatellite markers, we identified a region of homozygosity shared by all patients on 2q34, in a region harbouring the ABCA12 gene. Direct sequencing of genomic DNA derived from a patient failed to reveal any obviously pathogenic change in the coding sequence of this gene. In contrast, cDNA sequence analysis revealed the existence of a 163-bp-long deletion in exon 24, thus pointing to a splicing defect. Careful reanalysis of the genomic DNA sequence revealed apart from several known single-nucleotide polymorphisms, a hitherto unreported homozygous synonymous mutation in exon 24 (c.3456G>A; p.S1152S), which was found to lead to the formation of a novel splicing acceptor site. Synonymous mutations have been shown to uncommonly cause inherited disorders in humans. Here, we present the first example of a congenital form of ichthyosis resulting from such a genetic defect.
authors.affiliation: Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Tomer
authors.initials: T
authors.lastname: Goldsmith
authors.forename: Dana
authors.initials: D
authors.lastname: Fuchs-Telem
authors.forename: Shirli
authors.initials: S
authors.lastname: Israeli
authors.forename: Ofer
authors.initials: O
authors.lastname: Sarig
authors.forename: Gilly
authors.initials: G
authors.lastname: Padalon-Brauch
authors.forename: Reuven
authors.initials: R
authors.lastname: Bergman
authors.forename: Margarita
authors.initials: M
authors.lastname: Indelman
authors.forename: Eli
authors.initials: E
authors.lastname: Sprecher
authors.forename: Janna
authors.initials: J
authors.lastname: Nousbeck
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D018912:Arabs / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D016113:Ichthyosiform Erythroderma, Congenital / Q000235:genetics*; D007557:Israel; D008297:Male; D009154:Mutation; D010375:Pedigree
chemical_list: C473801:ABCA12 protein, human; D018528:ATP-Binding Cassette Transporters