Unidad de Investigacion, Hospital Universitario Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain.
Instituto Universitario de Enfermedades Tropicales y Salud Publica de Canarias (IUETSPC), Universidad de La Laguna, 38296 Santa Cruz de Tenerife, Spain.
Int J Mol Sci. 2023 May 8;24(9):8455. doi: 10.3390/ijms24098455.
Renal hypouricemia (RHUC) is a rare inherited disorder characterized by impaired urate reabsorption in the proximal tubule resulting in low urate serum levels and increased urate excretion. Some patients may present severe complications such as exercise-induced acute renal failure and nephrolithiasis. RHUC is caused by inactivating mutations in the (RHUC type 1) or (RHUC type 2) genes, which encode urate transporters URAT1 and GLUT9, respectively. In this study, our goal was to identify mutations associated with twenty-one new cases with RHUC through direct sequencing of and coding exons. Additionally, we carried out an SNPs-haplotype analysis to determine whether the rare variant c.374C>T; p.(T125M), which is recurrent in Spanish families with RHUC type 2, had a common-linked haplotype. Six intragenic informative SNPs were analyzed using PCR amplification from genomic DNA and direct sequencing. Our results showed that ten patients carried the mutation c.1400C>T; p.(T467M), ten presented the mutation c.374C>T, and one carried a new heterozygous mutation, c.593G>A; p.(R198H). Patients carrying the mutation c.374C>T share a common-linked haplotype, confirming that it emerged due to a founder effect.
肾脏尿酸排泄减少症（RHUC）是一种罕见的遗传性疾病，其特征是近端肾小管尿酸重吸收受损，导致血清尿酸水平降低和尿酸排泄增加。一些患者可能出现严重并发症，如运动诱发的急性肾衰竭和肾结石。RHUC 是由 （RHUC 型 1）或 （RHUC 型 2）基因的失活突变引起的，这两个基因分别编码尿酸转运蛋白 URAT1 和 GLUT9。在这项研究中，我们的目标是通过直接测序 和 编码外显子来鉴定与 21 例新 RHUC 病例相关的突变。此外，我们还进行了 SNP 单倍型分析，以确定在西班牙 RHUC 型 2 家族中反复出现的罕见 变体 c.374C>T; p.(T125M) 是否具有常见的连锁单倍型。使用从基因组 DNA 进行 PCR 扩增和直接测序分析了六个内含子信息性 SNP。我们的结果表明，10 名患者携带 突变 c.1400C>T; p.(T467M)，10 名患者携带 突变 c.374C>T，1 名患者携带新的 杂合突变 c.593G>A; p.(R198H)。携带 突变 c.374C>T 的患者共享一个常见的连锁单倍型，证实它是由于一个奠基者效应而出现的。
