Mitani Noriaki, Niwa Yoshimasa, Yamazaki Masaharu, Okamoto Yasuyuki
Central Clinical Laboratory, Nara Medical University, Kashihara.
Rinsho Byori. 2006 Jun;54(6):589-92.
Idiopathic renal hypouricemia is a hereditary disease characterized by abnormally increased renal excretion of urate. This disorder is primarily caused by a mutation of the SLC22A12 gene encoding human urate transporter 1 (URAT1). We recently encountered a case of severe hypouricemia (urate level: 0.5mg/dl in serum, 1.19g/l in urine), which was discovered when a 24-year-old male medical student was carrying out a practical examination of his own blood sample. The student was clinically healthy and showed no other abnormal laboratory findings, but his elder brother had a history of exercise-induced acute renal failure (ARF). DNA sequencing of the SLC22A12 gene demonstrated one nonsense mutation, W258X in this student. To confirm the genotype and for use in screening for W258X, we developed a polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) assay using a mismatched primer to introduce a new HinfI restriction site into the PCR products of exon 4. The genotype of our case was then confirmed as being heterozygous, with W258X and wild-type genes. We next used this PCR-RFLP assay to examine the frequency of W258X in 64 pairs of anonymous DNA and serum samples from various Japanese patients. Three patients were found to have W258X (all heterozygous). The allelic frequency of W258X was 2.34%. Considering that hypouricemia-related ARF is frequent in children and young adults, it may be worthwhile to screen for renal hypouricemia in these age groups. Our PCR-RFLP assay may be useful for this purpose.
特发性肾性低尿酸血症是一种遗传性疾病，其特征是肾脏尿酸排泄异常增加。这种疾病主要由编码人尿酸转运蛋白1（URAT1）的SLC22A12基因突变引起。我们最近遇到一例严重低尿酸血症（血清尿酸水平：0.5mg/dl，尿尿酸水平：1.19g/l），该病例是在一名24岁男性医学生对自己的血样进行实践检查时发现的。该学生临床健康，无其他异常实验室检查结果，但其哥哥有运动诱发急性肾衰竭（ARF）病史。对该学生的SLC22A12基因进行DNA测序，发现一个无义突变W258X。为了确认基因型并用于W258X的筛查，我们开发了一种聚合酶链反应（PCR）-限制性片段长度多态性（RFLP）检测方法，使用错配引物在第4外显子的PCR产物中引入一个新的HinfI限制性位点。随后确认我们病例的基因型为杂合子，含有W258X和野生型基因。接下来，我们使用这种PCR-RFLP检测方法检测了64对来自不同日本患者的匿名DNA和血清样本中W258X的频率。发现3例患者有W258X（均为杂合子）。W258X的等位基因频率为2.34%。鉴于儿童和年轻人中与低尿酸血症相关的ARF很常见，在这些年龄组中筛查肾性低尿酸血症可能是值得的。我们的PCR-RFLP检测方法可能对此有用。
