In other species: pig

Category: Homeostasis / metabolism phene

Possibly relevant human trait(s) and/or gene(s) (MIM number): 176100 (trait)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2005

Cross-species summary: Porphyrins are a class of organic compounds characterised by four pyrrole nuclei connected in a ring structure. When combined with iron, porphyrins form haem, which is a component of haemoglobin, cytochromes, catalases and peroxidases. Thus, porphyrins are constituents of many compounds that play a vital role in biological systems. The biosynthesis of porphyrins involves a six-step process, starting with aminolaevulinic acid (ALA) and ending with protoporphyrin. Each step is catalysed by an enzyme. A deficiency of any one of these enzymes results in a buildup of intermediates prior to the step for which the enzyme is lacking, and a deficiency of intermediates after that step. In much of the literature, these intermediates are loosely called porphyrins. Porphyria cutanea tarda results from a deficiency of the fourth enzyme, uroporphyrinogen decarboxylase, and a consequent buildup of intermediates (i.e. a buildup of porphyrins) that have been synthesised in the three previous steps.

History: This disorder in sheep was first reported by Nezamzadeh et al. (2005).

Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on homologous clinical signs in other species), Nezamzadeh et al. (2005) identified the causative mutation of this disorder in a family of German Blackface sheep as a missense base substitution (C>T) in the UROD gene, resulting in L131P at the active cleft site of the peptide.

Breed: Scottish Blackface (Sheep) (VBO_0001598).

Associated gene: