Congenital Porphyria in Swine

Yamashita, Chie; Shimazaki, Hideo; Miyake, Tsutomu; Saitoh, Masashi; Saheki, Yurio; Ishitani, R.

doi:10.1292/jvms1939.42.353

Cited by 6 publications

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“…Previously, cats who presented with brownish discolored teeth that fluoresced pink under UV light and had increased URO and COPRO concentrations were reported as having a "congenital porphyria" or CEP (24,25,30,31). However, the feline disease was inherited as an autosomal D 1 6 ( 9 -1 0 ) 3 8 1 -3 dominant trait, as it was in some pig models (21,23,32,33), whereas in humans and cattle the disease is inherited only as an autosomal recessive trait (2,22,32,34). Recently, this conundrum was clarified, because cats with the CEP-like phenotype and autosomal dominant inheritance were shown to actually have AIP (1).…”

Section: Discussionmentioning

confidence: 99%

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Feline Congenital Erythropoietic Porphyria: Two Homozygous UROS Missense Mutations Cause the Enzyme Deficiency and Porphyrin Accumulation

Clavero

Bishop

Giger

et al. 2010

Mol Med

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The first feline model of human congenital erythropoietic porphyria (CEP) due to deficient uroporphyrinogen III synthase (UROsynthase) activity was identified by its characteristic clinical phenotype, and confirmed by biochemical and molecular genetic studies. The proband, an adult domestic shorthair cat, had dark-red urine and brownish discolored teeth with red fluorescence under ultraviolet light. Biochemical studies demonstrated markedly increased uroporphyrinogen I in urine and plasma (2,650-and 10,700-fold greater than wild type, respectively), whereas urinary 5-aminolevulinic acid and porphobilinogen were lower than normal. Erythrocytic URO-synthase activity was <1% of mean wild-type activity, confirming the diagnosis and distinguishing it from feline phenocopies having acute intermittent porphyria. Sequencing of the affected cat's UROS gene revealed two missense mutations, c.140C>T (p.S47F) in exon 3 and c.331G>A (p.G111S) in exon 6, both of which were homozygous, presumably owing to parental consanguinity. Neither was present in 100 normal cat alleles. Prokaryotic expression and thermostability studies of the purified monomeric wild-type, p.S47F, p.G111S, and p.S47F/G111S enzymes showed that the p.S47F enzyme had 100% of wild-type specific activity but ~50% decreased thermostability, whereas the p.G111S and p.S47F/G111S enzymes had about 60% and 20% of wild-type specific activity, respectively, and both were markedly thermolabile. Molecular modeling results indicated that the less active/less stable p.G111S enzyme was further functionally impaired by a structural interaction induced by the presence of the S47F substitution. Thus, the synergistic interaction of two rare amino acid substitutions in the URO-synthase polypeptide caused the feline model of human CEP.

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Section: Discussionmentioning

confidence: 99%

“…Naturally occurring animal models of congenital porphyria with erythrodontia were described decades ago in cattle (20)(21)(22), pigs (21,23) and cats (24,25). A previously reported feline model had an autosomal dominant CEP-like phenotype (that is, erythrodontia) and elevated urinary and/or tissue PBG, URO and COPRO.…”

Section: Introductionmentioning

confidence: 99%