目的 探讨PAX2基因变异所致的1个慢性肾脏病(CKD)家系的遗传学特征。 方法 选取2018年8月15日至2021年7月5日于大理大学第一附属医院就诊的1个CKD家系4代共10人为研究对象。收集先证者的临床资料，并进行家系调查。应用全外显子组测序(WES)技术和生物信息学分析对先证者进行疑似致病基因筛选，应用Sanger测序进行家系验证。 结果 先证者为女性，年龄为41岁，确诊"慢性肾炎"4+年。尿常规提示尿蛋白(+)，血肌酐1 130 μmol/L，肾穿刺病理结果提示增生硬化性肾小球肾炎、中度肾小管间质病变及肾小动脉硬化。其姐姐、弟弟、妹妹和母亲为CKD 5期患者，除姐姐外均已去世，余家系成员未见异常。基因检测发现先证者及4名家系成员携带PAX2：c.167G>A错义变异。该变异与局灶节段性肾小球硬化相关，根据美国医学遗传学与基因组学学会(ACMG)相关指南评估为可能致病性变异(PS1+PP3+PP4)。 结论 PAX2：c.167G>A变异可能为该CKD家系的遗传学病因。 Objective To explore the genetic basis of a Chinese pedigree affected with chronic kidney disease (CKD). Methods A Chinese pedigree comprised of 10 individuals from four generation who had visited the First Affiliated Hospital of Dali University from August 15, 2018 to July 5, 2021 was selected as the study subject. Clinical data of the proband were collected, and a pedigree survey was conducted. The proband was subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis. Results The proband, a 41-year-old female, has been diagnosed with chronic nephritis for more than 4 years. Routine urinary examination showed urine protein (+ ) and blood creatinine of 1 130 μmol/L. Renal puncture revealed hyperplastic glomerulonephritis, moderate tubulointerstitial disease and renal arteriosclerosis. Her elder sister, younger brother, younger sister and mother were all diagnosed with CKD stages. Except for her elder sister, all of them had deceased, and no abnormality was found in the remainders. Genetic testing revealed that the proband and four family members had harbored a c. 467G>A missense variant of the PAX2 gene. The variant has been associated with focal segmental glomerulosclerosis and classified as likely pathogenic (PS1+ PP3+ PP4) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Conclusion The c. 167G>A variant of thePAX2 gene probably underlay the CKD in this Chinese pedigree.
Abstract
Objective To explore the genetic basis of a Chinese pedigree affected with chronic kidney disease (CKD). Methods A Chinese pedigree comprised of 10 individuals from four generation who had visited the First Affiliated Hospital of Dali University from August 15, 2018 to July 5, 2021 was selected as the study subject. Clinical data of the proband were collected, and a pedigree survey was conducted. The proband was subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis. Results The proband, a 41-year-old female, has been diagnosed with chronic nephritis for more than 4 years. Routine urinary examination showed urine protein (+ ) and blood creatinine of 1 130 μmol/L. Renal puncture revealed hyperplastic glomerulonephritis, moderate tubulointerstitial disease and renal arteriosclerosis. Her elder sister, younger brother, younger sister and mother were all diagnosed with CKD stages. Except for her elder sister, all of them had deceased, and no abnormality was found in the remainders. Genetic testing revealed that the proband and four family members had harbored a c. 467G>A missense variant of the PAX2 gene. The variant has been associated with focal segmental glomerulosclerosis and classified as likely pathogenic (PS1+ PP3+ PP4) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Conclusion The c. 167G>A variant of thePAX2 gene probably underlay the CKD in this Chinese pedigree.
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