FAN1基因c.1799A>T突变与巨核细胞性间质性肾炎的关联

Correlation between c.1799A>T mutation in FAN1 gene and karyomegalic interstitial nephritis

目的探究巨核细胞性间质性肾炎(KIN)与FAN1基因突变的关联性。方法2022年10月,发现一个家族聚集性肾炎家系。对家系成员进行全外显子组测序以确定候选基因,并通过Alpine分析、遗传变异判读和Sanger测序分析该基因。结果肾病家系先证者临床表型为肾炎,先证者母亲检出FAN1基因c.1799A>T突变。对家系中杂合性成员采用Sanger测序,也检测到相同的突变基因,依据美国医学遗传学与基因组学学会(ACMG)推荐指南,将其归类为意义不明的基因突变。本研究中的家系性肾炎表型与KIN部分相符。结论本研究中家系性肾炎的表型与FAN1基因c.1799A>T位点突变有密切关联。

Objective To explore the correlation between karyomegalic interstitial nephritis(KIN)and FAN1 gene mutations.Methods In October 2022,a family lineage of nephritis with familial aggregation was clinically confirmed in our department.The whole exome sequencings of the patients with nephritis were performed to identify candidate genes.The genetic pathogenicity was analyzed using Alpine analysis,gene variant interpretation,and Sanger sequencing analysis.Results The clinical phenotype of the patients from a family with nephropathy was nephritis.A c.1799A>T mutation in FAN1 gene was detected in the mother of the patients with nephritis.Sanger sequencing was performed on heterozygous members in the family,and the same mutated genes were also detected in a heterozygous member of this family.According to the recommended guidelines of American college of medical genetics and genomics(ACMG),it is classified as a gene mutation of unknown significance.The phenotype of familial nephritis in this study was partially consistent with that of KIN.Conclusion The phenotype of familial nephritis in this study is closely related to c.1799A>T site mutation in FAN1 gene.