Children's Hospital of Fudan University, 399 Wanyuan Road, Minhang District, Shanghai 201102, China.
BMC Nephrol. 2014 Jun 17;15:92. doi: 10.1186/1471-2369-15-92.
Primary hyperoxaluria type 1 is a rare autosomal recessive disease of glyoxylate metabolism caused by a defect in the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT) that leads to hyperoxaluria, recurrent urolithiasis, and nephrocalcinosis.
Two unrelated patients with recurrent urolithiasis, along with members of their families, exhibited mutations in the AGXT gene by PCR direct sequencing.
Two heterozygous mutations that predict truncated proteins, p.S81X and p.S275delinsRAfs, were identified in one patient. The p.S81X mutation is novel. Two heterozygous missense mutations, p.M1T and p.I202N, were detected in another patient but were not identified in her sibling. These four mutations were confirmed to be of paternal and maternal origin.
These are the first cases of primary hyperoxaluria type 1 to be diagnosed by clinical manifestations and AGXT gene mutations in mainland China. The novel p.S81X and p.I202N mutations detected in our study extend the spectrum of known AGXT gene mutations.
1 型原发性高草酸尿症是一种罕见的常染色体隐性疾病，由肝脏特异性过氧化物酶体酶丙氨酸：乙醛酸氨基转移酶（AGT）缺陷引起，导致高草酸尿症、复发性尿路结石和肾钙质沉着症。
两名患有复发性尿路结石的无关患者及其家族成员通过 PCR 直接测序发现 AGXT 基因突变。
在一名患者中发现了两个预测截短蛋白的杂合突变，p.S81X 和 p.S275delinsRAfs。p.S81X 突变是新的。另一名患者检测到两个杂合错义突变，p.M1T 和 p.I202N，但在其兄弟姐妹中未发现。这四个突变被证实是来自父亲和母亲的遗传。
这些是中国大陆首例通过临床表现和 AGXT 基因突变诊断的 1 型原发性高草酸尿症病例。本研究中检测到的新的 p.S81X 和 p.I202N 突变扩展了已知 AGXT 基因突变谱。
