Objectives: To review recent advances in our understanding of the genetic pathomechanisms of harlequin ichthyosis (HI) (the most devastating subtype of congenital ichthyoses) and its prenatal diagnosis and to discuss the possibility of future gene therapy.
Data source: PubMed search for articles about HI, its causative protein adenosine triphosphate-binding cassette A12 (ABCA12), and related molecules.
Study selection: English-language studies were selected if they provided useful information about the pathomechanisms of HI and ABCA lipid transporters.
Data synthesis: This article describes ABCA12 as a causative molecule involved in defects in HI, summarizes the known genetic disorders caused by genetic defects in ABCA lipid transporters, and highlights the prospects of prenatal diagnosis and gene therapy for HI.
Conclusions: Harlequin ichthyosis is caused by a serious functional deficiency of ABCA12. ABCA12 and ABCA3 are essential lipid transporters for human adaptation to a dry terrestrial environment. In clinical practice, information regarding the genetic defects and pathomechanisms underlying HI is important for precise diagnosis, genetic counseling, and prenatal diagnosis.