title: ABCA12 mutations and autosomal recessive congenital ichthyosis: a review of genotype/phenotype correlations and of pathogenetic concepts.
abstract: Mutations in ABCA12 have been described in autosomal recessive congenital ichthyoses (ARCI) including harlequin ichthyosis (HI), congenital ichthyosiform erythroderma (CIE), and lamellar ichthyosis (LI). HI shows the most severe phenotype. CIE and LI are clinically characterized by fine, whitish scales on a background of erythematous skin, and large, thick, dark scales over the entire body without serious background erythroderma, respectively. To date, a total of 56 ABCA12 mutations have been reported in 66 ARCI families including 48 HI, 10 LI, and 8 CIE families of African, European, Pakistani/Indian, and Japanese origin (online database: http://www.derm-hokudai.jp/ABCA12/). A total of 62.5% of reported ABCA12 mutations are expected to lead to truncated proteins. Most mutations in HI are truncation mutations and homozygous or compound heterozygous truncation mutations always results in HI phenotype. In CIE families, at least one mutation on each allele is typically a missense mutation. Combinations of missense mutations in the first ATP-binding cassette of ABCA12 underlie the LI phenotype. ABCA12 is a keratinocyte lipid transporter associated with lipid transport in lamellar granules, and loss of ABCA12 function leads to a defective lipid barrier in the stratum corneum, resulting in an ichthyotic phenotype. Recent work using mouse models confirmed ABCA12 roles in skin barrier formation.
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. akiyama@med.hokudai.ac.jp
authors.forename: Masashi
authors.initials: M
authors.lastname: Akiyama
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000818:Animals; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016113:Ichthyosiform Erythroderma, Congenital / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D017490:Ichthyosis, Lamellar / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D009154:Mutation; D010641:Phenotype; D011296:Prenatal Diagnosis; D012867:Skin / Q000473:pathology
chemical_list: C473801:ABCA12 protein, human; D018528:ATP-Binding Cassette Transporters