Zhang Yingying, Li Nannan, Lu Min, Lei Yumeng, Zhang Kaiqian, Liu Jishi
Department of Nephropathy and Rheumatology, Third Xiangya Hospital, Central South University, Changsha 410013.
Clinical Research Center for Critical Kidney Disease in Hunan Province, Changsha 410013, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2025 Apr 28;50(4):724-730. doi: 10.11817/j.issn.1672-7347.2025.240135.
Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare autosomal dominant hereditary disorder characterized by hyperuricemia, gout, impaired urinary concentration, and progressive renal failure. It is primarily caused by mutations in uromodulin () gene. This study reports a family with ADTKD in which whole-exome sequencing and Sanger sequencing identified a missense mutation in the gene, c.761A>C (p.H254P), present in both the proband and affected relatives. According to American College of Medical Genetics and Genomics (ACMG) guidelines, this variant is classified as likely pathogenic. The mutation results in an amino acid substitution that may impair UMOD protein folding and intracellular trafficking. gene mutations are associated with ADTKD, and genetic testing plays a vital role in the early diagnosis and treatment of this condition, highlighting its importance in the diagnosis of rare kidney diseases.
常染色体显性遗传性肾小管间质性肾病（ADTKD）是一种罕见的常染色体显性遗传性疾病，其特征为高尿酸血症、痛风、尿浓缩功能受损以及进行性肾衰竭。它主要由尿调节蛋白（UMOD）基因突变引起。本研究报告了一个患有ADTKD的家系，通过全外显子测序和桑格测序在该家系的先证者和患病亲属中均鉴定出UMOD基因的一个错义突变，即c.761A>C（p.H254P）。根据美国医学遗传学与基因组学学会（ACMG）的指南，该变异被分类为可能致病。该突变导致氨基酸替换，可能会损害UMOD蛋白的折叠和细胞内运输。UMOD基因突变与ADTKD相关，基因检测在该疾病的早期诊断和治疗中起着至关重要的作用，凸显了其在罕见肾病诊断中的重要性。
