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Pediatric Nephrology

, Volume 30, Issue 8, pp 1279–1287 | Cite as

Genetic abnormalities and prognosis in patients with congenital and infantile nephrotic syndrome

  • Onur Cil
  • Nesrin Besbas
  • Ali Duzova
  • Rezan Topaloglu
  • Amira Peco-Antić
  • Emine Korkmaz
  • Fatih Ozaltin
Original Article

Abstract

Background

Congenital nephrotic syndrome (CNS) and infantile nephrotic syndrome (INS) are caused primarily by mutations in genes that encode structural and regulatory proteins of the glomerular filtration barrier. The aim of this study was to determine genotype–phenotype correlations and prognosis in patients with CNS and INS.

Methods

NPHS1, NPHS2, LAMB2 and the eighth and ninth exons of WT1 were sequenced in 80 and 22 patients with CNS and INS, respectively. Genotype–phenotype correlations and survival were evaluated.

Results

Causative mutations were identified in 64.7 % of patients, of which NPHS1 mutations were the most common (37.4 %). The mutation detection rate was twofold higher in CNS patients than in INS patients (72.5 vs. 36.2 %). The most commonly mutated gene in CNS patients was NPHS1 (46.3 %) versus NPHS2 (13.6 %) and WT1 (13.6 %) in INS patients. NPHS2 mutations, female patients with NPHS1 mutations, and NPHS1 mutations affecting the transmembrane or intracellular domains of nephrin were associated with longer survival.

Conclusions

Based on our present findings, the likelihood of identification of a genetic cause decreases with increasing age at diagnosis. The underlying genetic abnormality should be identified as early as possible, as this knowledge will facilitate clinicians in their prognostic prediction and enable patients to receive appropriate genetic counseling.

Keywords

Congenital nephrotic syndrome Infantile nephrotic syndrome NPHS1 NPHS2 WT1 LAMB2 

Notes

Acknowledgments

We are grateful to the patients and their families for their participation in this study. This study received funding from the Scientific and Technological Research Council of Turkey (TÜBİTAK) (grant number 108S417) in the context of the PodoNet consortium supported by the European Research Area Network (E-RARE), European Community’s Seventh Framework Programme (FP7/2007-2013) (EURenOmics; grant 2012-305608) and The Scientific Research and Development Office of Hacettepe University (011A101003). The Nephrogenetics Laboratory at Hacettepe University, Faculty of Medicine, Department of Pediatric Nephrology, was established by the Hacettepe University Infrastructure Project (grant number 06A101008).

Conflict of interest statement

None.

Collaborators (in alphabetical order)

Adana: Gonul Parmaksiz, Aytul Noyan; Antalya: Arife Uslu Gokceoglu, Elif Comak; Ankara: Banu Celikel Acer, Birsin Ozcakar, Esra Baskin, Fatos Yalcinkaya, Mesiha Ekim, Nilgun Cakar, Rahime Renda, Yasar Kandur; Bosnia and Herzegovina: Danka Pokrajac; Gaziantep: Beltinge Demircioglu Kilic, Mithat Buyukcelik, Ayse Balat Istanbul: Cengiz Candan, Faruk Oktem, Harika Alpay, Mehmet Tasdemir, Meryem Benzer, Nilufer Goknar, Nurdan Yildiz, Nurver Akinci, Salim Caliskan; Izmir: Alper Soylu, Belde Kasap Demir, Demet Alaygut, Ebru Yilmaz, Meral Torun Bayram, Salih Kavukcu; Iran: Sonbol Ameli; Kayseri: Ismail Dursun, Kenan Yilmaz, Sibel Yel; Konya: Bulent Atas, Sevgi Pekcan, Yalcin Celik; Mersin: Ali Delibas; Serbia: Radovan Bogdanovic, Snezana Zulic; Syria: Bassam Saeed.

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Copyright information

© IPNA 2015

Authors and Affiliations

  • Onur Cil
    • 1
  • Nesrin Besbas
    • 1
  • Ali Duzova
    • 1
  • Rezan Topaloglu
    • 1
  • Amira Peco-Antić
    • 2
  • Emine Korkmaz
    • 3
  • Fatih Ozaltin
    • 1
    • 3
    • 4
    • 5
  1. 1.Department of Pediatric NephrologyHacettepe UniversityAnkaraTurkey
  2. 2.Nephrology Department, University Children’s HospitalUniversity of Belgrade School of MedicineBelgradeSerbia
  3. 3.Nephrogenetics LaboratoryHacettepe UniversityAnkaraTurkey
  4. 4.Center for Biobanking and GenomicsHacettepe UniversityAnkaraTurkey
  5. 5.Departments of Pediatric Nephrology and Rheumatology, Faculty of MedicineHacettepe UniversityAnkaraTurkey

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