English: Manifestation of harlequin-type ichthyosis is caused by total loss of ABCA12 function. This may occur by one of two different mechanisms: either both parents hand down the same ABCA12 mutation, resulting in a true homozygote for harlequin ichthyosis, or each parent hands down a different mutant ABCA12 allele, resulting in compound heterozygous dysfunction of the ABCA12 lipid transporter protein. Mutations resulting in harlequin ichthyosis are overwhelmingly caused by truncating mutations, such as nonsense mutations or deletions. Current literature suggests that it is highly unlikely that a missense mutation would result in severe enough protein dysfunction to cause manifestation of a harlequin phenotype.