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

J Dermatol. 2017 Aug;44(8):950-953. doi: 10.1111/1346-8138.13823. Epub 2017 Mar 11.

Abstract

Harlequin ichthyosis (HI) is the most severe form of autosomal recessive congenital ichthyosis, with a high mortality rate. Recent advances in neonatal care and the early administration of retinoids have improved the survival rate of HI. Here, we present a case of HI who was successfully treated with early administration of etretinate and showed good prognosis. Next-generation sequencing identified novel mutations of the ATP-binding cassette subfamily A member 12 gene (ABCA12), c.5884+4_+5delAA and c.7239G>A, which caused skipping of exons 39 and 48, respectively. Transcripts with exon 48 skipping, which cause a deletion in the second ATP-binding cassette of ABCA12, were dominantly expressed in the skin. Besides the early administration of etretinate, the differential expression of the mutant protein with limited segmental deletion of ABCA12 may be related to the favorable outcome of our patient.

Keywords: alternative splicing; autosomal recessive congenital ichthyosis; etretinate; harlequin ichthyosis; human ABCA12 protein.

Publication types

  • Case Reports

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • Alternative Splicing / genetics
  • Biopsy
  • Etretinate / therapeutic use
  • Exons / genetics
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Ichthyosis, Lamellar / drug therapy*
  • Ichthyosis, Lamellar / genetics*
  • Infant, Newborn
  • Keratolytic Agents / therapeutic use*
  • Male
  • Sequence Analysis, DNA
  • Sequence Deletion / genetics
  • Skin / pathology

Substances

  • ABCA12 protein, human
  • ATP-Binding Cassette Transporters
  • Keratolytic Agents
  • Etretinate