Primary hyperoxaluria in cats is caused by a mutation in the feline GRHPR gene

Abstract

Primary hyperoxaluria (PH) is a rare, inherited disease in humans resulting from mutations in the alanine:glyoxylate aminotransferase gene (PH1) or in the glyoxylate reductase (GRHPR) gene (PH2). A disease in cats, mimicking PH2, was described with an autosomal recessive mode of inheritance. Recently, we recognized lesions consistent with PH in kidneys from 3 kittens. Genomic DNA was extracted from 1 blood and 2 formalin-fixed kidney samples from the 3 affected kittens, from blood from the affected cats' sire, and from blood from 2 healthy unrelated cats. The 9 feline GRHPR exons and intronic donor-acceptor sites were amplified and sequenced. A point mutation G to A was identified at the acceptor site of intron 4. Affected cats were AA, normal cats GG, and the sire was heterozygous A/G. RNA from healthy, carrier, and affected cats was extracted and the GRHPR transcript sequenced revealing an exon 5 deletion in the affected transcript. The 89-bp deletion causes a frameshift and a premature stop codon 44 amino acids downstream, resulting in an anticipated 119 amino acids missing from the C-terminus of the affected cat protein. The unaffected cat expresses the normal transcript, whereas the carrier expressed both.