OMIA 000836-9913 : Protoporphyria in Bos taurus

In other species: chicken

Possibly relevant human trait(s) and/or gene(s) (MIM number): 177000

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 1998

Cross-species summary: Protoporphyrin is the last intermediate in the seven-step biosynthesis of haem from aminolaevulinic acid (ALA). The conversion of protoporphyrin to haem is catalised by the enzyme ferrochelatase. Protoporphyria is a disorder resulting from the buildup of protoporphyrin (and the other five, earlier intermediates [porphyrins] in this pathway: see the entry for porphyria, unclassified), due to the lack of this enzyme. Protoporphyrin is extremely photoreactive. Because of this, photosensitivity is the main clinical sign of this disorder.

Molecular basis: The report of the use of a DNA genotyping test by Healy et al. (1995), citing a personal communication from G.S. Johnson at the University of Missouri, implied that the molecular basis of this disorder within the gene for ferrochelatase had been determined by Dr Johnson. Jenkins et al. (1998) appear to have been the first to publicly report the molecular basis of this disorder. They did so by cloning and sequencing a very likely comparative candidate gene (based on the homologous human disorder), and reported a base substitution in the stop codon of the bovine ferrochelatase gene, that destroys that codon, resulting in an additional 27 amino acids in the peptide. To FN's knowledge, this is the first reported case in non-laboratory animals of the obliteration of a stop codon by a base substitution: a stop-loss or extension mutation.

Genetic testing: Citing a personal communication from G.S. Johnson at the University of Missouri, Healy et al. (1995) report using a DNA test on hair roots to genotype cattle for this disorder.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
FECH ferrochelatase Bos taurus 24 NC_037351.1 (56822085..56787248) FECH Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective.

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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
Blonde d'Aquitaine Limousin Protoporphyria FECH extension (stop-lost) UMD3.1 24 g.57298883G>T c.1250G>T p.*417Lext*27 1998 9784594 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool; Breed information kindly provided or confirmed by Matt McClure and Jennifer McClure from "Understanding Genetics and Complete Genetic Disease and Trait Definition (Expanded 2016 Edition)" (https://www.icbf.com/wp/?page_id=2170)

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2015 Anon. :
Erythropoietic protoporphyria in Limousin calves. Vet Rec 177:432-5, 2015. Pubmed reference: 26515350. DOI: 10.1136/vr.h5598.
McAloon, C.G., Doherty, M.L., O'Neill, H., Badminton, M., Ryan, E.G. :
Bovine congenital erythropoietic protoporphyria in a crossbred limousin heifer in Ireland. Ir Vet J 68:15, 2015. Pubmed reference: 26140209. DOI: 10.1186/s13620-015-0044-3.
2002 Armstrong, S.C., Jonsson, N.N., Barrett, D.C. :
Bovine congenital erythrocytic protoporphyria in a Limousin calf bred in the UK Veterinary Record 150:608-610, 2002. Pubmed reference: 12036245.
Pence, ME., Liggett, AD. :
Congenital erythropoietic protoporphyria in a Limousin calf. J Am Vet Med Assoc 221:277-9, 240, 2002. Pubmed reference: 12118595.
1998 Jenkins, M.M., LeBoeuf, R.D., Ruth, G.R., Bloomer, J.R. :
A novel stop codon mutation (X417L) of the ferrochelatase gene in bovine protoporphyria, a natural animal model of the human disease. Biochim Biophys Acta 1408:18-24, 1998. Pubmed reference: 9784594.
1995 Buchanan, M., Crawshaw, W.M. :
Bovine congenital erythropoietic protoporphyria in a pedigree Limousin heifer Veterinary Record 136:640, 1995. Pubmed reference: 7571274.
Healy, P.J., Dennis, J.A., Moule, J.F. :
Use of hair root as a source of DNA for the detection of heterozygotes for recessive defects in cattle Australian Veterinary Journal 72:392, 1995. Pubmed reference: 8599573.
Shibuya, H., Nonneman, D., Tamassia, M., Allphin, O.L., Johnson, G.S. :
The coding sequence of the bovine ferrochelatase gene. Biochim Biophys Acta 1231:117-20, 1995. Pubmed reference: 7640290.
1993 Healy, P.J., Dennis, J.A. :
Inherited Enzyme Deficiencies in Livestock Veterinary Clinics of North America - Food Animal Practice 9:55-63, 1993. Pubmed reference: 8457930.
1992 Healy, P.J., Camilleri, L., Poulos, V., Hart, K.G., Kemp, B.J., Moore, R.E., Dooley, J., Warner, M. :
Protoporphyria in Limousin Cattle Australian Veterinary Journal 69:144-145, 1992. Pubmed reference: 1642600.
1991 Lauvergne, J.J., Pinault, L. :
Hereditary Protoporphyria in French Limousin Cattle - 1st Results Genetics Selection Evolution 23:339-343, 1991.
Schelcher, F., Delverdier, M., Bezille, P., Cabanie, P., Espinasse, J. :
Observation on Bovine Congenital Erythrocytic Protoporphyria in the Blonde Daquitaine Breed Veterinary Record 129:403-407, 1991. Pubmed reference: 1767483.
Straka, J.G., Hill, H.D., Krikava, J.M., Kools, A.M., Bloomer, J.R. :
Immunochemical Studies of Ferrochelatase Protein - Characterization of the Normal and Mutant Protein in Bovine and Human Protoporphyria American Journal of Human Genetics 48:72-78, 1991. Pubmed reference: 1985464.
Troyer, D.L., Ayers, J., Wollen, H., Leipold, H.W., Cook, J.E. :
Gross, microscopic and ultrastructural lesions of protoporphyria in Limousin calves. Zentralbl Veterinarmed A 38:300-5, 1991. Pubmed reference: 1907789.
1990 Bloomer, J.R., Straka, J.G., Hill, H., Weimer, M.K., Ruth, G.R. :
Comparison of Bile Porphyrin Concentrations in Cattle and Human Beings with Protoporphyria American Journal of Veterinary Research 51:1144-1146, 1990. Pubmed reference: 2389893.
1987 Bloomer, JR., Hill, HD., Morton, KO., Anderson-Burnham, LA., Straka, JG. :
The enzyme defect in bovine protoporphyria. Studies with purified ferrochelatase. J Biol Chem 262:667-71, 1987. Pubmed reference: 3805002.
1982 Bloomer, JR., Morton, KO., Reuter, RJ., Ruth, GR. :
Bovine protoporphyria: documentation of autosomal recessive inheritance and comparison with the human disease through measurement of heme synthase activity. Am J Hum Genet 34:322-30, 1982. Pubmed reference: 7072720.
1981 Sassa, S., Schwartz, S., Ruth, G. :
Accumulation of protoporphyrin IX from delta-aminolevulinic acid in bovine skin fibroblasts with hereditary erythropoietic protoporphyria. A gene-dosage effect. J Exp Med 153:1094-101, 1981. Pubmed reference: 6788885.
1979 Brenner, DA., Bloomer, JR. :
Comparison of human and bovine protoporphyria. Yale J Biol Med 52:449-54, 1979. Pubmed reference: 392959.
1977 Ruth, GR., Schwartz, S., Stephenson, B. :
Bovine protoporphyria: the first nonhuman model of this hereditary photosensitizing disease. Science 198:199-201, 1977. Pubmed reference: 905823.
1976 Schwartz, S., O'Connor, N., Stephenson, BD., Anderson, AS., Johnson, LW., Johnson, J. :
Turnover of erythrocyte protoporphyrin, with special reference to bovine porphyria and iron deficiency anemia. Ann Clin Res 8 Suppl 17:203-12, 1976. Pubmed reference: 1008492.

Edit History


  • Created by Frank Nicholas on 26 Nov 2005
  • Changed by Frank Nicholas on 09 Dec 2011
  • Changed by Frank Nicholas on 04 Sep 2012
  • Changed by Frank Nicholas on 28 Aug 2016