COMBINED IMMUNE DEFICIENCY AND RENAL PHENOTYPE ASSOCIATED WITH PLCE1 GENE VARIANT
DOI:
https://doi.org/10.69656/pjp.v21i3.1851Keywords:
CRP, DNA Sequencing, Flow cytometery, Nephrotic Syndrome, PLCE1 geneAbstract
Background: Congenital Nephrotic Syndrome (CNS) is a paediatric kidney disease that is defined by massive protein loss in the urine, hypoalbuminemia, and hyperlipidemia. Mutations in PLCE1 are associated with autosomal recessive form of nephrotic syndrome associated with elevated T-cells. Methods: A two-month-old female patient from a Pakistani family suffering from recurrent renal infections with fever and cough was investigated in this study. Laboratory tests including renal function test, lipid profile, lymphocyte subset analysis using flow cytometry, serum immunoglobulin level and blood complete picture were performed. After detailed clinical evaluation, whole blood samples were collected in EDTA tubes for genetic analysis. Results: Complete blood count (CBC) showed low haemoglobin levels and lymphocytosis. Flow cytometery revealed elevated CD4/CD8 T-cells. Low serum immunoglobulin levels were observed. Genetic analysis revealed a missense mutation [c.6790A>G; (p.Lys2264Glu)] in the gene PLCE1. Conclusion: The current study describes a novel homozygous genetic mutation in PLCE1 gene. Clinical investigations revealed disease features partially fulfilling the criteria of inherited nephrotic syndrome.
Pak J Physiol 2025;21(3):7-10, DOI: https://doi.org/10.69656/pjp.v21i3.1851
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References
Ha TS. Genetics of hereditary nephrotic syndrome: a clinical review. Korean J Pediatr 2017;60(3):55–63.
Bierzy Bierzynska A, McCarthy HJ, Soderquest K, Sen ES, Colby E, Ding WY, et al. Genomic and clinical profiling of a national nephrotic syndrome cohort advocates a precision medicine approach to disease management. Kidney Int 2017;91(4):937–47.
Fr??il? VG, Lupu?oru G, Sorohan BM, Obri?c? B, Mocanu V, Lupu?oru M, et al. Nephrotic Syndrome: From Pathophysiology to Novel Therapeutic Approaches. Biomedicines 2024;12(3):569.
Horinouchi T, Nozu K, Iijima K. An updated view of the pathogenesis of steroid-sensitive nephrotic syndrome. Pediatr Nephrol 2022;37(9):1957–65.
Trautmann A, Lipska-Zi?tkiewicz BS, Schaefer F. Exploring the clinical and genetic spectrum of steroid resistant nephrotic syndrome: The Podonet Registry. Front Pediatr 2018;6:200.
Elbeltagi YAH, El Din El Kersh MM, Fathy HM, Kamel NAS. Study of steroid-resistant nephrotic syndrome: A single center experience. Egypt Pediatr Assoc Gaz 2024;72:35.
Popa L, Balgradean M, Croitoru A. Long-term study in children with steroid-resistant nephrotic syndrome progressing to end-stage renal disease. Maedica (Bucur) 2022;17:271–6.
Kopp JB, Anders HJ, Susztak K, Podesta MA, Remuzzi G, Hildebrandt F, et al. Podocytopathies. Nat Rev Dis Primers 2020;6:68.
Hackl A, Zed SE, Diefenhardt P, Binz-Lotter J, Ehren R, Weber LT. The role of the immune system in idiopathic nephrotic syndrome. Mol Cell Pediatr 2021;8(1):18.
Campbell RE, Thurman JM. The immune system and idiopathic nephrotic syndrome. Clin J Am Soc Nephrol 2022;17(12):1823–34.
Lipska-Zi?tkiewicz BS, Ozaltin F, Hölttä T, Bockenhauer D, Bérody S, Levtchenko E, et al. Genetic aspects of congenital nephrotic syndrome: a consensus statement from the ERKNet–ESPN inherited glomerulopathy working group. Eur J Hum Genet 2020;28(10):1368–78.
Cason RK, Chambers E, Tu T, Chryst-Stangl M, Huggins K, Lane BM, et al. Genetic risk variants for childhood nephrotic syndrome and corticosteroid response. Front Pediatr 2023;11:1248733.
Liu L, Wang H, Zhao B, Liu X, Sun Y, Mao Y. Nomogram to predict the progression of patients with primary membranous nephropathy and nephrotic syndrome. Int Urol Nephrol 2022;54(2):331–41.
Yu S, Choi WI, Choi YJ, Kim HY, Hildebrandt F, Gee HY. PLCE1 regulates the migration, proliferation, and differentiation of podocytes. Exp Mol Med 2020;52:594–603.
National Center for Biotechnology Information (NCBI). PLCE1 phospholipase C epsilon 1 [Internet]. Bethesda (MD): National Library of Medicine (US); 2025 [updated: 2025 Mar 8; cited 8 Mar 2025]. Available from: https://www.ncbi.nlm.nih.gov/gene/51196
Kelley GG, Reks SE, Ondrako JM, Smrcka AV. Phospholipase C (epsilon): a novel Ras effector. EMBO J 2001;20(4):743–54.
Lopez I, Mak EC, Ding J, Hamm HE, Lomasney JW. A novel bifunctional phospholipase C that is regulated by G?12 and stimulates the Ras/mitogen-activated protein kinase pathway. J Biol Chem 2001;276(4):2758–65.
Verma PR, Patil P. Nephrotic syndrome: a review. Cureus 2024;16(2):e53923.
Strazza M, Azoulay-Alfaguter I, Peled M, Smrcka AV, Skolnik EY, Srivastava S, et al. PLC?1 regulates SDF-1 ?-induced lymphocyte adhesion and migration to sites of inflammation. Proc Natl Acad Sci USA 2017;114(10):2693–8.
Hu XE, Jia J, Yang Z, Chen S, Xue J, Duan S, et al. PLCE1 polymorphisms are associated with gastric cancer risk: The changes in protein spatial structure may play a potential role. Front Genet 2021;12:714915.
Mount DB, Pollak MR. Molecular and Genetic Basis of Renal Disease E-Book: A Companion to Brenner and Rector’s The Kidney. Elsevier Health Sciences; 2007.
Xue W, Zhu M, Wang Y, He J, Zheng L. Association between PLCE1 rs2274223 A>G polymorphism and cancer risk: proof from a meta-analysis. Sci Rep 2015;5:7986.
Strazza M, Adam K, Smrcka AV, Lerrer S, Mor A. PLC?1 suppresses tumor growth by regulating murine T cell mobilization. Clin Exp Immunol 2020;200(1):53–60.
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Copyright (c) 2025 Nida Shafi, Maryam, Imran, Hira , Irfan, Irfan Raza

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