Identification of NPHS1 Genetic Variations in Cohort of Egyptian Patients with Congenital Nephrotic Syndrome


  • Amira Samy Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Giza, Egypt
  • Rasha Elkaffas Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Giza, Egypt
  • Fatina Fadel Department of Pediatrics, Faculty of Medicine, Cairo University, Giza, Egypt
  • Nehad Mosaad Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Giza, Egypt
  • Hanan Madani Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Giza, Egypt



Congenital nephrotic disease, NPHS1, Nephrin, Molecular findings, Diagnosis


Introduction: Autosomal recessive variations in NPHS1 gene represent common cause of congenital nephrotic syndrome (CNS). The disease is characterized by considerable proteinuria presenting in the first 90days of life. CNS has a poor outcome and usually leads to end stage renal disease by 2-3 years of life.   NPHS1 encodes the protein nephrin, expressed in inter-podocyte slit diaphragm. Aim of work: The main objective of this cross-sectional study was to perform the analysis of the NPHS1 gene in 24 Egyptian patients with CNS aiming to determine the molecular cause of the disease and to detect their phenotype/genotype correlations. Methods: Polymerase chain reaction followed by direct sequencing of exons (3,4,6,7,18,19) of NPHS1 gene was performed in 24 neonates with CNS with median age 25 days (1-90 day). Results:  three pathogenic variants were detected in five patients. They were one frame shift variant in exon 19, one missense de novo variant in exon 6 and one In-frame deletion variant in exon 4. Three benign variants were seen in seven patients in exon and intron 3. Conclusion: although the number of patient included in the study is small, but the results of the study presented de novo likely pathogenic mutation in exon 6 not reported before in 2 patients and 2 reported pathogenic variants. Molecular diagnosis is advised to be performed early in the diagnosis of CNS to avoid unnecessary immunesupp-ression and start early suitable treatment.


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Bérody S, Heidet L, Gribouval O, Harambat J, Niaudet P, Baudouin V, et al. Treatment and outcome of congenital nephrotic syndrome. Nephrol Dial Transpl. 2018(3):458-67. PMid:29474669 DOI:

Sharief SN, Hefni NA, Alzahrani WA, Nazer II, Bayazeed MA, Alhasan KA, et al. Genetics of congenital and infantile nephrotic syndrome. World J Pediatr. 2019;15(2):198-203. PMid:30721404 DOI:

Wang JJ, Mao JH. The etiology of congenital nephrotic syndrome: Current status and challenges. World J Pediatr. 2016;12(2):149-58. PMid:26961288 DOI:

Sadowski CE, Lovric S, Ashraf S, Pabst WL, Gee HY, Kohl S, et al. A single gene cause in 29.5% of cases of steroid-resistant nephrotic syndrome. J Am Soc Nephrol. 2015;26(6):1279-89. PMid:25349199 DOI:

Mann N, Braun D, Amann K, Tan W, Shril S, Connaughton DM, et al. Whole-exome sequencing enables a precision medicine approach for kidney transplant recipients. J Am Soc Nephrol. 2019;30(2):201-15. PMid:30655312 DOI:

Ha TS. Genetics of hereditary nephrotic syndrome: A clinical review. Korean J Pediatr. 2017;60(3):55-63. PMid:28392820 DOI:

Lenkerri U, Manniko M, McCready P, Lamerdin J, Gribouval O, Niaudet P, et al. Structure of the gene for congenital nephrotic syndrome of the Finnish type (NPHS1) and characterization of mutations. Am J Hum Genet. 1999;64(1):51-61. PMid:9915943 DOI:

Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977;74(12):5463-7. PMid:271968 DOI:

Dunnen JT, Antonarakis SE, Dalgeish R, Maglott DR, Hart RK, Greenblatt MS, et al. HGVS recommendations for the description of sequence variants: 2016 update. Hum Mutati. 2016;37(6):564-9. PMid:26931183 DOI:

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology. Genet Med. 2015;17(5):405-24. PMid:25741868 DOI:

Aya K, Shimizu J, Ohtomo Y, Satomura K, Suzuki H, Yan K, et al. NPHS1 gene mutation in Japanese patients with congenital nephrotic syndrome. Nephrol Dial Transplant. 2009;24(8):2411-4. PMid:19321760 DOI:

Kamphans T, Sabri P, Zhu N, Heinrich V, Mundlos S, Robinson PN, et al. Filtering for compound heterozygous sequence variants in non-consanguineous pedigrees. PLoS One. 2013;8(8):e70151. PMid:23940540 DOI:

Miyai T, Aya K, Takaiwa M. Functional analysis of NPHS1 mutations in Japanese patients. Histol Histopathol. 201429(2):279-84. PMid:24142548

Schoeb DS, Chernin G, Heeringa SF, Matejas V, Held S, Vega-Warner V, et al. Nineteen novel NPHS1 mutations in a worldwide cohort of patients with congenital nephrotic syndrome (CNS). Nephrol Dial Transplant. 2010;25(9):2970-6. PMid:20172850 DOI:

Santin S, Bullich G, Tazon-Vega B, García-Maset R, Giménez I, Silva I, et al. Clinical utility of genetic testing in children and adults with steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol. 2011;6(5):1139-48. PMid:21415313 DOI:

Al-Hamed M, Al-Sabban E, Al-Mojalli H, Al-Harbi N, Faqeih E, Al Shaya H, et al. A molecular genetic analysis of childhood nephrotic syndrome in a cohort of Saudi Arabian families. J Hum Genet.2013;58(7):480-9. PMid:23595123 DOI:

Nguyen TK, Pham VD, Nguyen TH, Pham TK, Nguyen TQ, Nguyen HH. Three novel mutations in the NPHS1 gene in Vietnamese patients with congenital nephrotic syndrome. Case Rep Genet 2017;2017:2357282. PMid:28392951 DOI:

Machuca E, Benoit G, Nevo F, Tête MJ, Gribouval O, Pawtowski A, et al. Genotype-phenotype corre lations in non- Finnish congenital nephrotic syndrome. J Am Soc Nephrol. 2010;21(7):1209-17. DOI:




How to Cite

Samy A, Elkaffas R, Fadel F, Mosaad N, Madani H. Identification of NPHS1 Genetic Variations in Cohort of Egyptian Patients with Congenital Nephrotic Syndrome. Open Access Maced J Med Sci [Internet]. 2022 Jan. 14 [cited 2023 Mar. 28];10(A):84-9. Available from:

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