ABCA12 mutations are known to underlie the three major types of autosomal recessive congenital ichthyoses: harlequin ichthyosis, lamellar ichthyosis and congenital ichthyosiform erythroderma.
We confirmed that ABCA12 defects cause congested lipid secretion in cultured HI keratinocytes and succeeded in obtaining the recovery of LG lipid secretion after corrective gene transfer of ABCA12.
This article reviews current opinions on the patho-mechanisms of ABCA12 action in HI and potential therapeutic interventions based on targeted molecular therapy and gene therapy strategies.
We report the case of an infant with novel heterozygous mutations in ABCA12 who exhibited features and a clinical course more consistent with congenital ichthyosiform erythroderma than harlequin ichthyosis.
Using whole exome sequencing, we identified in a child with congenital exfoliative erythroderma, hypotrichosis, severe nail dystrophy and failure to thrive, two heterozygous mutations in ABCA12 (c.2956C>T, p.R986W; c.5778+2T>C, p. G1900Mfs*16), a gene known to be associated with two forms of ichthyosis, autosomal recessive congenital ichthyosis, and harlequin ichthyosis.
Until the identification of ABCA12 as the causative gene, prenatal diagnosis (PND) for HI had been performed by electronmicroscopic observation of fetal skin biopsy samples.
Sequencing of the ABCA12 gene, which maps within the minimal region defined by homozygosity mapping, revealed disease-associated mutations, including large intragenic deletions and frameshift deletions in 11 of the 12 screened individuals with HI.
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.
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.
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.
The present patient demonstrates that rapid diagnosis of HI by ABCA12 expression analysis and mutation detection, and early commencement of systemic retinoid therapy are crucial to significantly improving an HI patient's prognosis.