Original article

Genetic diagnosis and clinical analysis of congenital dysfibrinogenemia with polycystic disease: a case report and literature review

Expand
  • a. Department of Laboratory Medicine, Shanghai 200025, China
    b. Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

Received date: 2023-03-09

  Online published: 2024-01-25

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.

Cite this article

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 . DOI: 10.16138/j.1673-6087.2023.05.004

References

[1] Dell KM, Matheson M, Hartung EA, et al. Kidney disease progression in autosomal recessive polycystic kidney disease[J]. J Pediatr, 2016, 171: 196-201.
[2] Bergmann C, Guay-Woodford LM, Harris PC, et al. Polycystic kidney disease[J]. Nat Rev Dis Primers, 2018, 4(1):50.
[3] Harris PC, Torres VE. Polycystic kidney disease, autosomal dominant[DB/OL]. 2022. https://www.ncbi.nlm.nih.gov/books/NBK1246/.
[4] Lanktree MB, Chapman AB. New treatment paradigms for ADPKD: moving towards precision medicine[J]. Nat Rev Nephrol, 2017, 13(12): 750-768.
[5] Cornec-Le Gall E, Alam A, Perrone RD. Autosomal dominant polycystic kidney disease[J]. Lancet, 2019, 393(10174): 919-935.
[6] Neerman-Arbez M, de Moerloose P, Casini A. Laboratory and genetic investigation of mutations accounting for congenital fibrinogen disorders[J]. Semin Thromb Hemost, 2016, 42(4): 356-365.
[7] Richard M, Celeny D, Neerman-Arbez M. Mutations accounting for congenital fibrinogen disorders[J]. Semin Thromb Hemost, 2022, 48(8): 889-903.
[8] Casini A, Neerman-Arbez M, Ari?ns RA, et al. Dysfibrinogenemia: from molecular anomalies to clinical manifestations and management[J]. J Thromb Haemost, 2015, 13(6): 909-919.
[9] Casini A, Blondon M, Lebreton A, et al. Natural history of patients with congenital dysfibrinogenemia[J]. Blood, 2015, 125(3): 553-561.
[10] Mangolini A, de Stephanis L, Aguiari G. Role of calcium in polycystic kidney disease[J]. World J Nephrol, 2016, 5(1): 76-83.
[11] Harris PC, Torres VE. Genetic mechanisms and signaling pathways in autosomal dominant polycystic kidney disease[J]. J Clin Invest, 2014, 124(6): 2315-2324.
[12] Bergmann C. Recent advances in the molecular diagnosis of polycystic kidney disease[J]. Expert Rev Mol Diagn, 2017, 17(12): 1037-1054.
[13] Chapman AB, Devuyst O, Eckardt KU, et al. Autosomal-dominant polycystic kidney disease (ADPKD)[J]. Kidney Int, 2015, 88(1): 17-27.
[14] Obeidova L, Elisakova V, Stekrova J, et al. Novel mutations of PKD genes in the Czech population with autosomal dominant polycystic kidney disease[J]. BMC Med Genet, 2014, 15: 41.
[15] Trujillano D, Bullich G, Ossowski S, et al. Diagnosis of autosomal dominant polycystic kidney disease using efficient PKD1 and PKD2 targeted next-generation sequencing[J]. Mol Genet Genomic, 2014, 2(5): 412-421.
[16] Rahbari-Oskoui F, Williams O, Chapman A. Mechanisms and management of hypertension in autosomal dominant polycystic kidney disease[J]. Nephrol Dial Transplant, 2014, 29(12): 2194-2201.
[17] Nauli SM, Jin X, Hierck BP. The mechanosensory role of primary cilia in vascular hypertension[J]. Int J Vasc Med, 2011: 376281.
[18] Kocyigit I, Eroglu E, Gungor O. Clinical problems in hemodialysis patients with autosomal dominant polycystic kidney disease[J]. Semin Dial, 2018, 31(3): 268-277.
[19] Rozenfeld MN, Ansari SA, Shaibani A, et al. Should patients with autosomal dominant polycystic kidney disease be screened for cerebral aneurysms?[J]. AJNR Am J Neuroradiol, 2014, 35(1): 3-9.
[20] Perrone RD, Malek AM, Watnick T. Vascular complications in autosomal dominant polycystic kidney disease[J]. Nat Rev Nephrol, 2015, 11(10): 589-598.
[21] Etminan N, Rinkel GJ. Unruptured intracranial aneurysms: development, rupture and preventive management[J]. Nat Rev Neurol, 2016, 12(12): 699-713.
[22] Cagnazzo F, Gambacciani C, Morganti R, et al. Intracranial aneurysms in patients with autosomal dominant polycystic kidney disease: prevalence, risk of rupture, and management[J]. Acta Neurochir (Wien), 2017, 159(5): 811-821.
[23] Qian Q, Younge BR, Torres VE. Retinal arterial and venous occlusions in patients with ADPKD[J]. Nephrol Dial Transplant, 2007, 22(6): 1769-1771.
[24] Kuo IY, Chapman AB. Polycystins, ADPKD, and cardiovascular disease[J]. Kidney Int Rep, 2019, 5(4): 396-406.
[25] Gabow PA, Duley I, Johnson AM. Clinical profiles of gross hematuria in autosomal dominant polycystic kidney disease[J]. Am J Kidney Dis, 1992, 20(2): 140-143.
[26] Colbert GB, Elrggal ME, Gaur L, et al. Update and review of adult polycystic kidney disease[J]. Dis Mon, 2020, 66(5): 100887.
[27] Nishiura JL, Neves RF, Eloi SR, et al. Evaluation of nephrolithiasis in autosomal dominant polycystic kidney disease patients[J]. Clin J Am Soc Nephrol, 2009, 4(4): 838-844.
[28] Torres VE, Wilson DM, Hattery RR, et al. Renal stone disease in autosomal dominant polycystic kidney disease[J]. Am J Kidney Dis, 1993, 22(4): 513-519.
[29] Gambaro G, Fabris A, Puliatta D, et al. Lithiasis in cystic kidney disease and malformations of the urinary tract[J]. Urol Res, 2006, 34(2): 102-107.
[30] Moist LM, Churchill DN, House AA, et al. Regular monitoring of access flow compared with monitoring of venous pressure fails to improve graft survival[J]. J Am Soc Nephrol, 2003, 14(10): 2645-2653.
[31] Schwab SJ, Oliver MJ, Suhocki P, et al. Hemodialysis arteriovenous access: detection of stenosis and response to treatment by vascular access blood flow[J]. Kidney Int, 2001, 59(1): 358-362.
[32] Hsieh MY, Cheng CH, Chen CH, et al. The association of long-term blood pressure variability with hemodialysis access thrombosis[J]. Front Cardiovasc Med, 2022, 9:881454.
[33] Haverkate F, Samama M. Familial dysfibrinogenemia and thrombophilia[J]. Thromb Haemost, 1995, 73(1): 151-161.
[34] Casini A, How I treat dysfibrinogenemia[J]. Blood, 2021, 138(21): 2021-2030.
[35] Vakalopoulou S, Mille-Baker B, Mumford A, et al. Fibrinogen Bbeta14 Arg—>Cys: further evidence for a role in thrombosis[J]. Blood Coagul Fibrinolysis, 1999, 10(7): 403-408.
Outlines

/