We reported two neonates with homozygous mutations in ABCA12 consistent with harlequin ichthyosis who survived to discharge home with intensive care and without use of systemic retinoids.
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.
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.
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.
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.
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.
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.
ABCA12 mutations are known to underlie the three major types of autosomal recessive congenital ichthyoses: harlequin ichthyosis, lamellar ichthyosis and congenital ichthyosiform erythroderma.
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.
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.
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).
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.