常染色体显性局灶节段肾小球硬化一家系INF2基因及临床特征

目的 分析1个常染色体显性局灶节段肾小球硬化（AD-FSGS）家系的临床特征及可能的致病基因。方法 调查1个中国AD-FSGS家系，收集临床资料，绘制家系图谱，并对家系中所有成员进行尿液筛查，并留取其外周血，对其中尿液筛查异常的2个家庭7名成员进行ACTN4、TRPC6和INF2基因所有外显子，以及WT1基因外显子8和9直接测序。生物信息学初步分析突变位点对蛋白结构和功能的影响。结果该家系共有4代，27名成员，现有成员23名。发病者5例，女性3例，男性2例，平均发病年龄26.9岁。临床资料分析显示，该家系临床特点符合AD-FSGS诊断。7名成员中未发现ACTN4、TRPC6基因所有外显子和WT1基因外显子8、9有致病性突变，其中5例发病者INF2基因外显子8均有纯合缺失突变，缺失的碱基为CCCCACCCCCAC（c.1249delCCCCACCCCCAC,p.T420_P423del），缺失在外显子8第274～285位点，该位点突变既往未见报道。c.1249delCCCCACCCCCAC位于INF2表达分子inverted formin 重要的Diaphanous抑制结构域（DID）编码区。结论 INF2基因外显子8上的杂合缺失突变可能是该家系AD-FSGS患者的致病原因，c.1249delCCCCACCCCCAC是引起AD-FSGS的一种新型突变。

Clinical characteristics and INF2 gene mutation analysis in a family with autosomal dominant focal segmental glomerulosclerosis

Objective To investigate pathogenic gene of autosomal dominant focal segmental glomerulosclerosis （AD-FSGS）. Methods Clinical data of an AD-FSGS family were collected and analyzed. Urine screening was given to all members of the family. Peripheral blood was taken from all members of the family. Sequencing of all exons of ACTN4, TRPC6 and 1NF2 and exon 8, 9 of WT1 was performed for 7 members of the family. Changes in protein structure and function caused by mutant coding sequence were analyzed by online NCBI （ The National Center for Biotechnology Information）. Results The clinical feature of the family was consistent with characteristics of AD-FSGS. No pathogenic mutation in ACTN4, TRPC6 and WT1 was found. Five patients of the family had a deletion mutation （ c. 1249delCCCCACCCCCAC, p. T420_P423del） in INF2, which had not been reported before. This new mutation is located in the diaphanous inhibitory domain of the protein encoded by INF2. Conclusions c. 1249delCCCCACCCCCAC is a new mutation and may be the causal mutation of AD-FSGS in the family.