Sydney School of Veterinary Science, Faculty of Science, Valentine Charlton Cat Centre, University of Sydney, Camperdown, New South Wales, 2006, Australia.
Sydney School of Veterinary Science, Faculty of Science, University of Sydney, Camperdown, New South Wales, 2006, Australia.
Anim Genet. 2023 Aug;54(4):576-580. doi: 10.1111/age.13318. Epub 2023 Mar 27.
Xanthinuria is a clinically significant form of urolithiasis in cats with poor clinical outcomes and limited treatment options. In humans, xanthinuria has an autosomal recessive mode of inheritance, with variants in xanthine dehydrogenase (XDH) and molybdenum cofactor sulfurase (MOCOS) responsible for cases. While causative genetic variants have not been identified in the domestic cat, a recessive mode of inheritance has been suggested. DNA was extracted from EDTA-stabilised blood obtained from a Domestic Shorthair cat with clinically confirmed xanthinuria. Whole-genome sequencing and variant assessment in XDH and MOCOS identified XDH:c.2042C>T (XDH:p.(A681V)) as a candidate causative variant for xanthinuria in this cat. The variant is located in a highly conserved part of the molybdenum-pterin co-factor domain, responsible for catalysing the hydroxylation of hypoxanthine to xanthine and uric acid. Variants in this domain of XDH have been shown to disrupt enzyme function and to cause xanthinuria in other species. When assessed in the wider cat population, the variant had an allele frequency of 15.8%, with 0.9% of the animals assessed homozygous for the alternative allele. Cats diagnosed with xanthinuria should be tested for this variant to validate its clinical relevance in the wider population.
黄嘌呤尿症是猫结石病的一种临床显著形式，临床结果不佳，治疗选择有限。在人类中，黄嘌呤尿症为常染色体隐性遗传模式，黄嘌呤脱氢酶（XDH）和钼辅因子硫酶（MOCOS）的变异导致发病。虽然在家猫中尚未确定致病遗传变异，但已提示为隐性遗传模式。从一只经临床确诊患有黄嘌呤尿症的家短毛猫采集 EDTA 稳定的血液，提取 DNA。对 XDH 和 MOCOS 进行全基因组测序和变异评估，发现 XDH:c.2042C>T（XDH:p.(A681V)）是该猫黄嘌呤尿症的候选致病变异。该变异位于钼-喋呤辅酶结构域的高度保守部分，负责催化次黄嘌呤羟化为黄嘌呤和尿酸。该 XDH 结构域的变异已被证明会破坏酶的功能，并导致其他物种的黄嘌呤尿症。在更广泛的猫群体中评估时，该变异的等位基因频率为 15.8%，评估的动物中有 0.9%为该替代等位基因的纯合子。应检测诊断为黄嘌呤尿症的猫是否存在该变异，以验证其在更广泛人群中的临床相关性。
