Mandrile G, Robbiano A, Giachino D F, Sebastiano R, Dondi E, Fenoglio R, Stratta P, Caruso M R, Petrarulo M, Marangella M, De Marchi M
Departement of Clinical and Biological Sciences, Medical Genetics Unit, S. Luigi Hospital, University of Torino, Regione Gonzole 10, 10043, Orbassano (TO), Italy.
Urol Res. 2008 Dec;36(6):309-12. doi: 10.1007/s00240-008-0162-4. Epub 2008 Nov 5.
We report the clinical and genetic study of a primary hyperoxaluria type I (PH1) family with two sisters homozygous for p.Gly170Arg who are still asymptomatic at age 29 and 35, and two brothers, also homozygous for the same mutation, who are affected since age 27 and 30. The clear sex difference observed in this family and in others reported in the literature fits well with the prevalence of males over females in the Italian registry. In the KO model of PH1, only male mice develop renal stones, suggesting that the sex difference may affect both oxalate production and stone formation. A likely mechanism is the sex-related expression of glycolate oxidase shown in experimental animals. The stable isotope method recently developed by Huidekoper and van Woerden for in vivo assessment of the endogenous oxalate production could help to clarify the issue in humans.
我们报告了一个I型原发性高草酸尿症（PH1）家系的临床和遗传学研究。该家系中有两名姐妹，她们为p.Gly170Arg纯合子，在29岁和35岁时仍无症状；还有两名兄弟，同样为该突变纯合子，分别在27岁和30岁时发病。在这个家系以及文献中报道的其他家系中观察到的明显性别差异，与意大利登记处男性患病率高于女性的情况相符。在PH1的基因敲除模型中，只有雄性小鼠会形成肾结石，这表明性别差异可能会影响草酸盐生成和结石形成。一个可能的机制是实验动物中显示的乙醇酸氧化酶的性别相关表达。Huidekoper和van Woerden最近开发的用于体内评估内源性草酸盐生成的稳定同位素方法，可能有助于阐明人类的这一问题。
