Genotype and Phenotype of Renal Hypouricemia: A Single-Center Study from China.

IF 4.1 3区医学 Q1 GENETICS & HEREDITY

Molecular Diagnosis & Therapy Pub Date : 2024-01-01 Epub Date: 2023-11-16 DOI:10.1007/s40291-023-00683-w

Lijun Mou, Lina Zhu, Xujiao Chen, Ying Hu, Hong Zhu, Ying Xu

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引用次数: 0

Abstract

Background: Renal hypouricemia (RHUC), a rare inherited disorder characterized by impaired uric acid reabsorption and subsequent profound hypouricemia, occurs mainly due to variants in SLC22A12 or SLC2A9. Only anecdotal cases and one small-scale RHUC screening study have been reported in the Chinese population.

Methods: A total of 19 patients with RHUC from 17 unrelated families were recruited from our center. The medical history, clinical manifestations, biochemical exam, and clinical outcomes were collected. Next-generation sequencing-based targeted gene sequencing or whole exon sequencing was performed.

Results: A total of 22 variants in SLC22A12 or SLC2A9 were found in 19 patients. The variant c.944G>A (p.W315X) in SLC2A9 was identified in three patients. Three variants c.165C>A (p.D55E), c.1549_1555delGAGACCC (p.E517Rfs*17), and c.1483T>C (p.W495R) in SLC22A12 and three variants c.1215+1G>A (splicing variant), c.643A>C (p.T215P), and c.227C>A (p.S76X) in SLC2A9 were novel. A proportion of 10 out of 19 patients presented with exercise-induced acute kidney injury (EIAKI). The renal outcome was favorable. Five patients had nephrolithiasis, in whom three had hypercalciuria.

Conclusion: The current study reported six novel variants in SLC22A12 and SLC2A9 genes of Chinese patients with RHUC. The variant c.944G>A (p.W315X) in SLC2A9 may be common in Chinese patients. EIAKI is the main clinical phenotype associated with RHUC in our cohort, with a favorable outcome. Hypercalciuria presented in some RHUC patients is a new finding.

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肾性低尿酸血症基因型和表型:一项来自中国的单中心研究。

背景:肾性低尿酸血症(RHUC)是一种罕见的遗传性疾病，主要由SLC22A12或SLC2A9基因变异引起，其特征是尿酸重吸收受损，随后出现严重的低尿酸血症。在中国人群中，仅报道了轶事病例和一项小规模RHUC筛查研究。方法:从本中心招募17个无血缘关系家庭的19例RHUC患者。收集患者的病史、临床表现、生化检查及临床结果。进行基于下一代测序的靶向基因测序或全外显子测序。结果:19例患者中发现SLC22A12或SLC2A9共22个变异。SLC2A9的c.944G>A (p.W315X)变异在3例患者中被鉴定出来。SLC22A12的C . 165c >A (p.D55E)、C . 1549_1555delgagaccc (p.E517Rfs*17)、C . 1483t >C (p.W495R)和SLC2A9的C .1215+1G>A(剪接变体)、C . 643a b> C (p.T215P)、C . 227c >A (p.S76X)是新发现的。19例患者中有10例出现运动性急性肾损伤(EIAKI)。肾脏预后良好。5例患者有肾结石，其中3例有高钙尿症。结论:本研究报道了中国RHUC患者SLC22A12和SLC2A9基因的6个新变异。SLC2A9的c.944G>A (p.W315X)变异可能在中国患者中很常见。在我们的队列中，EIAKI是与RHUC相关的主要临床表型，预后良好。一些RHUC患者出现高钙尿是一项新发现。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Diagnosis & Therapy 医学-药学

CiteScore

7.80

自引率

2.50%

发文量

审稿时长

>12 weeks

期刊介绍： Molecular Diagnosis & Therapy welcomes current opinion articles on emerging or contentious issues, comprehensive narrative reviews, systematic reviews (as outlined by the PRISMA statement), original research articles (including short communications) and letters to the editor. All manuscripts are subject to peer review by international experts.