New UMOD gene mutation: a familial study of juvenile hyperuricemia nephropathy
10.3760/cma.j.cn441217-20200226-00131
- VernacularTitle:新 UMOD基因突变：家族性青少年高尿酸血症肾病家系研究
- Author:
Yuanying LIU
1
;
Dan WANG
;
Jinjin FAN
;
Wenfang CHEN
;
Wei CHEN
;
Zhijian LI
;
Xin WANG
Author Information
1. 中山大学附属第一医院肾内科 国家卫健委及广东省肾脏病重点实验室，广州 510080
- From:
Chinese Journal of Nephrology
2020;36(10):737-743
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the etiology, clinicopathological changes and genetic variation characteristics of familial juvenile hyperuricemia nephropathy (FJHN) through pedigree investigation and gene test conducted on a patient with FJHN.Methods:Clinical data of the proband family members were collected, routine pathological examination of the proband kidney tissue was conducted, and the expression of the Uromodulin (UMOD) protein in the proband kidney tissue was detected by immunofluorescence staining. Peripheral blood specimens of proband and their relatives were collected, and gene sequencing analysis related to urinary system diseases including UMOD was performed by double-stranded DNA probe gene capture and high-throughput sequencing. Results:Seven family members in the family were involved and the inheritance method was consistent with autosomal dominant inheritance. Among the seven affected individuals only a 3-year-old child didn't show any clinical abnormalities. All of the remaining six patients had hyperuricemia accompanied with renal dysfunction and three of them were end-stage renal disease and two of them died of uremia. Proband renal pathological results showed chronic tubulointerstitial lesions and focal glomerular sclerosis with no obvious deposition of immune complexes. Immunofluorescent staining showed that strong positive signals of UMOD protein accumulated in the tubular epithelial cells, which was very specific and could be used to differentiate FJHN from other interstial nephritis. A total of four patients including the proband were tested and all had found heterozygous mutation c.377G>A of UMOD gene, a new missense mutation located on exon 3. Conclusion:Involved patients in this family present a typical autosomal dominant inheritance pattern, clinically manifested as hyperuricemia with early renal function impairment, renal pathology manifested as non-immune complex-mediated glomerular sclerosis and renal interstitial fibrosis, and there is abnormal accumulation of UMOD protein in renal tubular epithelial cells. Genetic testing shows a new gene locus mutation c.377G>A, confirming the diagnosis of FJHN. Patients with unexplained hyperuricemia and characteristic pathological changes should undergo renal tissue fluorescent staining of UMOD protein, which may be a simple and feasible method to detect the abnormality of UMOD protein.
