一个家族性多囊肾伴纤维蛋白原缺陷症家系的基因诊断、临床特征及文献回顾

doi:10.16138/j.1673-6087.2023.05.004

摘要/Abstract

摘要： 目的分析一个家族性多囊肾伴纤维蛋白原缺陷症家系的基因诊断及相关临床表现，研究其发病机制并为临床治疗提供指导。方法将患者外周血样本中分离出基因组DNA，进行全外显子组测序，Sanger法对多囊肾病1（polycystic kidney disease 1，PKD1）和纤维蛋白原β链（fibrinogen beta chain，FGB）基因突变结果进行验证。肾脏超声检查多囊肾，Clauss法检测血浆纤维蛋白原活性，免疫比浊法检测血浆纤维蛋白原抗原。检索国内外2种疾病相关的文献并进行分析总结。结果 PKD1在第15外显子发生c.6586C>T，p.Q2196X杂合无义突变，FGB在第2外显子发生 c.130C>T，p.R44C杂合错义突变。患者超声结果诊断为多囊肾，纤维蛋白原抗原正常（2.3 g/L）、活性降低（1.25 g/L）。文献检索结果显示2种突变在国外均有报道，在国内首次报道。结论 PKD1 p.Q2196X和FGB p.R44C杂合突变分别导致该患者的多囊肾和异常纤维蛋白原血症。目前临床表型主要由多囊肾引起，应以多囊肾治疗为主，定期随访，保护肾功能。

关键词: 纤维蛋白原缺陷症, 纤维蛋白原, 多囊肾, 基因突变

Abstract: Objective To analyze the genetic diagnosis and related clinical manifestations of a Chinese pedigree with inherited dysfibrinogenemia and polycystic kidney disease, investigate the molecular mechanism of the diseases and provide guidance for clinical treatment. Methods Ultrasonography was performed to examine polycystic kidney disease. The activity and antigen of fibrinogen in plasma were measured by Clauss and immunoturbidimetry methods, respectively. The genomic DNA was extracted from peripheral venous blood of the patient. Mutations in whole-exome genotypes were screened with the next generation sequencing technology, and were verified through PCR and Sanger sequencing technology. Domestic and foreign literature related to two diseases were searched and reviewed. Results The polycystic kidney disease was diagnosed by conducting ultrasound examination. The plasma fibrinogen activity level in the patient was reduced, while fibrinogen antigen level was normal. The sequencing results showed the patient had nonsense heterozygous nonsense mutation c.6586C>T, p.Q2196X in polycystic kidney disease 1(PKD1) gene and missense heterozygous mutation c.130C>T，p.R44C in fibrinogen beta chain(FGB) gene. The two mutations had been reported in foreign publications, but they were reported for the first time in China. Conclusions PKD1 p.Q2196X heterozygous nonsense mutation in the patients leads to polycystic kidney disease and the dysfibrinogenemia of the proband is caused by FGB p.R44C heterozygous mutation. At present, the clinical phenotype of the proband is mainly related to polycystic kidney disease. Treatment should be focused on renal function protection in polycystic kidney disease, and the patients should receive regular follow-up care.

Key words: Dysfibrinogenemia, Fibrinogen, Polycystic disease, Gene mutation

中图分类号:

R692

周礼扬, 张春丽, 丁秋兰, 李娅. 一个家族性多囊肾伴纤维蛋白原缺陷症家系的基因诊断、临床特征及文献回顾[J]. 内科理论与实践, 2023, 18(05): 328-333.

ZHOU Liyang, ZHANG Chunli, DING Qiulan, LI Ya. Genetic diagnosis and clinical analysis of congenital dysfibrinogenemia with polycystic disease: a case report and literature review[J]. Journal of Internal Medicine Concepts & Practice, 2023, 18(05): 328-333.

图/表 5

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