page_title: Harlequin-type ichthyosis
section_title: Cause
hierarchical_section_title: Harlequin-type ichthyosis / Cause
caption_attribution_description: 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.
context_page_description: Harlequin-type ichthyosis is a genetic disorder that results in thickened skin over nearly the entire body at birth. The skin forms large, diamond-shaped plates that are separated by deep cracks. These affect the shape of the eyelids, nose, mouth, and ears and limit movement of the arms and legs. Restricted movement of the chest can lead to breathing difficulties. These plates fall off over several weeks. Other complications can include premature birth, infection, problems with body temperature, and dehydration. The condition is the most severe form of ichthyosis, a group of genetic disorders characterised by scaly skin.
  Harlequin-type ichthyosis is caused by mutations in the ABCA12 gene. This gene codes for a protein necessary for transporting lipids out of cells in the outermost layer of skin. The disorder is autosomal recessive and inherited from parents who are carriers. Diagnosis is often based on appearance at birth and confirmed by genetic testing. Before birth, amniocentesis or ultrasound may support the diagnosis.
  There is no cure for the condition. Early in life, constant supportive care is typically required.
context_section_description: Harlequin-type ichthyosis is caused by a loss-of-function mutation in the ABCA12 gene. This gene is important in the regulation of protein synthesis for the development of the skin layer. Mutations in the gene cause impaired transport of lipids in the skin layer and may also lead to shrunken versions of the proteins responsible for skin development. Less severe mutations result in a collodion membrane and congenital ichthyosiform erythroderma-like presentation.
  ABCA12 is an ATP-binding cassette transporter (ABC transporter), which are members of a large family of proteins that hydrolyze ATP to transport cargo across cell membranes. ABCA12 is thought to be a lipid transporter in keratinocytes necessary for lipid transport into lamellar granules during the formation of the lipid barrier in the skin.
caption: Two genetic mechanisms that can result in harlequin-type ichthyosis
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