title: Non-bullous congentital ichthyosiform erythroderma associated with homozygosity for a novel missense mutation in an ATP binding domain of ABCA12.
abstract: A Mutations in the gene encoding the ABCA12 protein are associated with different subtypes of autosomal recessive congenital ichthyosis (ARCI), including Harlequin ichthyosis (HI), lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE). Disruption of ABCA12 lead to perturbed lipid transport in lamellar granules and a defective intercellular lipid layer of the stratum corneum. We have identified a large consanguineous Pakistani family affected by NCIE. Autozygosity mapping showed that affected individuals are homozygous for the ABCA12 gene region. Subsequent mutation screening revealed a homozygous c.4676G>T transition in all five affected family members. The mutation results in a novel p.G1559V substitution within the first nucleotide binding domain of ABCA12. The combined results support that an ABCA12 missense mutation, despite its location in a functional domain, may be associated with a mild ichthyosis phenotype. Furthermore, our findings increase the mutational spectrum in ABCA12 associated with ARCI of diagnostic and prognostic importance.
authors.affiliation: National Institute for Biotechnology and Genetic Engineering, Faisalabad, Pakistan.
authors.forename: Sadia
authors.initials: S
authors.lastname: Nawaz
authors.forename: Muhammad
authors.initials: M
authors.lastname: Tariq
authors.forename: Ilyas
authors.initials: I
authors.lastname: Ahmad
authors.forename: Naveed Altaf
authors.initials: NA
authors.lastname: Malik
authors.forename: Shahid Mahmood
authors.initials: SM
authors.lastname: Baig
authors.forename: Niklas
authors.initials: N
authors.lastname: Dahl
authors.forename: Joakim
authors.initials: J
authors.lastname: Klar
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D017490:Ichthyosis, Lamellar / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree
chemical_list: C473801:ABCA12 protein, human; D018528:ATP-Binding Cassette Transporters