OMIA 001176-9940 : Porphyria cutanea tarda in Ovis aries

In other species: pig

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

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: German Blackface.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
urod uroporphyrinogen decarboxylase Ovis aries 1 NC_040252.1 (20326467..20329800) urod Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
German Blackface Porphyria cutanea tarda urod missense Oar_v3.1 1 g.19437840T>C c.392T>C p.L131P rs429214636 2005 16026339 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

Reference


2005 Nezamzadeh, R., Seubert, A., Pohlenz, J., Brenig, B. :
Identification of a mutation in the ovine uroporphyrinogen decarboxylase (UROD) gene associated with a type of porphyria. Anim Genet 36:297-302, 2005. Pubmed reference: 16026339. DOI: 10.1111/j.1365-2052.2005.01301.x.

Edit History


  • Created by Frank Nicholas on 15 Nov 2005
  • Changed by Frank Nicholas on 09 Dec 2011
  • Changed by Frank Nicholas on 03 Dec 2012
  • Changed by Frank Nicholas on 28 Sep 2015
  • Changed by Frank Nicholas on 11 Aug 2016
  • Changed by Frank Nicholas on 12 Dec 2017