Categories: Homeostasis / metabolism phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 222748 (trait) , 613326 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0009111: dihydropyrimidinuria

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2012

Species-specific symbol: DHP deficiency

History: Chang et al. (2012) reported the first feline case.

Inheritance: Because only one case has been reported, there are no segregation data. However, since the disorder has been shown to be due to an enzyme deficiency, it is almost certain to have autosomal recessive inheritance.

Molecular basis: On the strength of the clinical evidence implying a deficiency of the enzyme dihydropyrimidinase (see section on Clinical features), Chang et al. (2012) used the direct candidate gene approach and sequenced the DPYS gene encoding this enzyme, in the affected cat, showing that "the cat was homozygous for the missense mutation c.1303G>A (p.G435R) in exon 8, which corresponds to a known mutation in a human patient with DHP deficiency."

Clinical features: As reported by Chang et al. (2012), "A gas chromatographic–mass spectrometric analysis of urinary metabolic substances showed the presence of large amounts of dihydrouracil and dihydrothymine and moderate amounts of uracil and thymine, suggesting DHP deficiency".

Pathology: Genotyping 1000 Japanese cats for this mutation revealed no copies of the allele, suggesting that it must be a relatively new mutation.

Associated gene: