ABCA12 mutations are known to underlie the three major types of autosomal recessive congenital ichthyoses: harlequin ichthyosis, lamellar ichthyosis and congenital ichthyosiform erythroderma.
A case of harlequin ichthyosis with compound heterozygous mutations in ABCA12 was successfully managed with intensive neonatal care and endotracheal intubation and without oral retinoids.
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).
Autosomal recessive congenital ichthyosis (ARCI4B [OMIM #242500]), also known as harlequin ichthyosis, presents at birth with extreme hyperkeratosis and thick-fissured plaques, leading to tightness of the skin around the eyes, mouth, ears, chest, abdomen, and extremities.
Case of harlequin ichthyosis with a favorable outcome: Early treatment and novel, differentially expressed, alternatively spliced transcripts of the ATP-binding cassette subfamily A member 12 gene.
Here we generated an ethylnitrosourea mutagenic HI pig model (named Z9), which carries a novel deep intronic mutation IVS49-727 A>G in the ABCA12 gene, resulting in abnormal mRNA splicing and truncated protein production.
Improved understanding of the genetic basis of HI indicates that genetic screening for candidate gene mutations related to HI, particularly mutations in the adenosine triphosphate binding-cassette transporter ABCA12, may prove beneficial in prenatal diagnosis.
In fact, loss of ABCA12 function leads to a defective lipid barrier in the stratum corneum, resulting in the HI phenotype and ABCA12 is a known keratinocyte lipid transporter associated with lipid transport in lamellar granules.
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.
Mutations in the gene encoding a member of the ABCA transporter family, ABCA12, have been linked to harlequin ichthyosis, but the molecular function of the protein is unknown.
One of these components, ABCA12, has recently been shown to be 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 the HI phenotype.