Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Department of Pediatrics, Peking University First Hospital, Beijing, China.
Kidney Blood Press Res. 2019;44(4):743-753. doi: 10.1159/000501458. Epub 2019 Aug 9.
Primary hyperoxaluria type 3 (PH3) is a rare autosomal recessive disorder that affects glyoxylate metabolism. PH3 is caused by defects in 4-hydroxy-2-oxoglutarate aldolase, which is encoded by the HOGA1 gene. However, only 3 cases of PH3 have been described in Asians until today. This study aimed to determine the clinical and mutation spectra of patients from mainland China with PH3.
We applied targeted next-generation sequencing to four non-consanguineous, unrelated Chinese families with PH3 to identify the genes hosting disease-causing mutations. This approach was confirmed by Sanger sequencing.
Five patients (2 boys and 3 girls) from four unrelated Chinese families were admitted because of kidney stones. Five HOGA1 gene sequence mutations were detected, including two novel mutations, c.811C>T (p.R271C) and c.812G>A (p.R271H). These compound heterozygous mutations were detected in a female PH3 patient (patient 4). Other patients included 2 boys who had heterozygous c.834_834+1GG>TT and c.834G>A (p.A278A) mutations (patients 1 and 2), a girl with homozygous c.834G>A (p.A278A) mutation (patient 3), and a girl with heterozygous c.834_834+1GG>TT and c.346C>T (p.Q116X) mutations (patient 5). The mutations in the c.834_834+1 region, including c.834G>A, c.834+1G>T, and c.834_834+1GG>TT, account for 5/8 of alleles in our study and 3/4 of alleles reported among Chinese patients. All patients in this study received hyperhydration and urine alkalinization treatment.
Five PH3 cases were reported. Potential mutation hot spot region (c.834_834+1) in the Chinese population and two novel mutations were found.
原发性高草酸尿症 3 型（PH3）是一种罕见的常染色体隐性遗传疾病，影响乙醛酸代谢。PH3 是由 4-羟基-2-氧代戊二酸醛缩酶缺陷引起的，该酶由 HOGA1 基因编码。然而，直到今天，亚洲仅报道了 3 例 PH3 病例。本研究旨在确定中国大陆 PH3 患者的临床和突变谱。
我们应用靶向下一代测序技术对 4 个非近亲、无关的 PH3 中国家庭进行分析，以鉴定致病突变基因。该方法通过 Sanger 测序进行了验证。
来自 4 个无关中国家庭的 5 名患者（2 名男孩和 3 名女孩）因肾结石而入院。在 5 名患者中检测到 5 种 HOGA1 基因突变，包括 2 种新突变，c.811C>T（p.R271C）和 c.812G>A（p.R271H）。这些复合杂合突变在一名 PH3 女性患者（患者 4）中被发现。其他患者包括 2 名男孩，他们分别携带杂合 c.834_834+1GG>TT 和 c.834G>A（p.A278A）突变（患者 1 和 2），一名女孩携带纯合 c.834G>A（p.A278A）突变（患者 3），以及一名女孩携带杂合 c.834_834+1GG>TT 和 c.346C>T（p.Q116X）突变（患者 5）。c.834_834+1 区域的突变，包括 c.834G>A、c.834+1G>T 和 c.834_834+1GG>TT，占本研究中 8 个等位基因的 5/8 和中国患者报告的 4 个等位基因的 3/4。本研究中所有患者均接受了水化和尿液碱化治疗。
报告了 5 例 PH3 病例。在中国人群中发现了潜在的突变热点区域（c.834_834+1）和 2 种新突变。
