Analysis of Genotype and Phenotype in the Calculi Family Lineage
10.3870/j.issn.1004-0781.2025.04.015
- VernacularTitle:结石症家系的基因型和表型分析
- Author:
Wenpei LIANG
1
;
Yonghua HE
;
Jinyun PU
;
Xueqing MA
;
Panpan SHAO
;
Liru QIU
Author Information
1. 华中科技大学同济医学院附属同济医院儿童肾脏专科,武汉 430030
- Publication Type:Journal Article
- Keywords:
Kidney stones;
Gallstones;
Cystinuria;
SLC3A1 gene;
Whole exome sequencing
- From:
Herald of Medicine
2025;44(4):589-595
- CountryChina
- Language:Chinese
-
Abstract:
Objective Through molecular genetics analysis of a calculi family lineage,this study aims to explore its pathogenesis and the association between genotypes and phenotypes.Methods A retrospective analysis was conducted on a calculi family lineage admitted to Tongji Hospital,affiliated with Tongji Medical College,Huazhong University of Science and Technology.Clinical data and peripheral blood samples of the affected children and some family members were collected.Whole exome sequencing was performed,followed by Sanger sequencing to validate the candidate variants.Results Among the 38 family members across four generations,10 members were diagnosed with calculi disease.The second generation,member 2(Ⅱ-2),third generation,member 2(Ⅲ-2),and third generation,member 4(Ⅲ-4)suffered from recurrent multiple kidney stones and gallstones.The second generation,member 6(Ⅱ-6),second generation,member 13(Ⅱ-13),and third generation,member 5(Ⅲ-5)had recurrent multiple kidney stones alone,while first generation,member 2(Ⅰ-2),second generation,member 4(Ⅱ-4),second generation,member 8(Ⅱ-8),and second generation,member 11(Ⅱ-11)only had gallstones.No other family members exhibited any signs of kidney or gallbladder involvement.Ⅱ-2 was diagnosed in 2018 with end-stage renal disease stage 5,grade 3 hypertension and gallstones,urinary amino acid high-performance liquid chromatography analysis indicated elevated urinary cystine.This member had a history of recurrent multiple kidney stones and recurrent urinary tract infections for over 30 years,with multiple histories of ureteroscopic stone removal.Genetic analysis revealed that Ⅱ-2,Ⅲ-2,Ⅲ-4,Ⅲ-5 and Ⅳ-1 all carry a heterozygous mutation in exon 10 of the solute carrier family 3 member 1(SLC3A1)gene,c.1889G＞A(p.Gly630Asp).The third generation,member 1(Ⅲ-1),and fourth generation,member 2(Ⅳ-2),are wild type.This mutation shows a phenomenon of family co-segregation.Conclusions The heterozygous mutation of SLC3A1 gene,c.1889G＞A,may be the genetic cause of calculi disease in multiple members of this family lineage.Recurrent multiple kidney stones and/or gallstones require high attention to genetic etiology.It is recommended to perform genetic analysis on calculi family lineages and patients with early-onset calculi disease.
