Journal of Heredity Advance Access originally published online on June 16, 2009
Journal of Heredity 2009 100(Supplement 1):S2-S7; doi:10.1093/jhered/esp038
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This article appears in the following Journal of Heredity issue: Symposium Issue: Fourth International Conference on Advances in Canine and Feline Genomics and Inherited Diseases, Saint Malo, Brittany, France, 21-24 May 2008. [View the issue table of contents]
Original Articles |
Primary Hyperoxaluria in Cats Is Caused by a Mutation in the Feline GRHPR Gene
From the Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853 (Goldstein RE, Narala, and Sabet); the Department of Biomedical Sciences College of Veterinary Medicine, Cornell University, Ithaca, NY 14853 (McDonough); and the James A. Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853 (Goldstein O)
Address correspondence to Richard E. Goldstein at the address above, or e-mail: rg225{at}cornell.edu.
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.
Key Words: feline calcium oxalate • feline genetics • nephrocalcinosis • primary hyperoxaluria
Corresponding Editor: Marilyn Menotti-Raymond
Received November 25, 2008
Revised May 14, 2009
Accepted May 15, 2009