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Mutational analysis of the PLCE1 gene in steroid resistant nephrotic syndrome
  1. Olivia Boyer1,2,
  2. Geneviève Benoit1,3,
  3. Olivier Gribouval1,
  4. Fabien Nevo1,
  5. Audrey Pawtowski4,
  6. Ilmay Bilge5,
  7. Zelal Bircan6,
  8. Georges Deschênes7,
  9. Lisa M Guay-Woodford8,
  10. Michelle Hall9,
  11. Marie-Alice Macher7,
  12. Kenza Soulami10,
  13. Constantinos J Stefanidis11,
  14. Robert Weiss12,
  15. Chantal Loirat7,
  16. Marie-Claire Gubler1,
  17. Corinne Antignac1,4,13
  1. 1Inserm, U983, Hôpital Necker-Enfants Malades, Paris, France
  2. 2Assistance publique-Hôpitaux de Paris (AP-HP), Service de Néphrologie Pédiatrique, Centre de Référence des Maladies Rénales Héréditaires, Hôpital Necker-Enfants Malades, Paris, France
  3. 3Service de Néphrologie Pédiatrique, CHU Sainte-Justine, Université de Montréal, Canada
  4. 4Assistance Publique-Hôpitaux de Paris (AP-HP), Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France
  5. 5Department of Pediatrics, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey
  6. 6Department of Pediatric Nephrology, Kocaeli University Hospital, Kocaeli, Turkey
  7. 7Assistance publique-Hôpitaux de Paris (AP-HP), Service de Néphrologie Pédiatrique, Hôpital Robert Debré, Paris, France
  8. 8Department of Genetics, UAB Center for Clinical and Translational Science, Birmingham, Alabama, USA
  9. 9Department of Pediatric Nephrology, Hôpital Universitaire des Enfants - Reine Fabiola, Université Libre de Bruxelles (ULB), Brussels, Belgium
  10. 10Service de Néphrologie Dialyse Transplantation, CHU Ibn Rochd, Casablanca, Maroc
  11. 11Department of Pediatric Nephrology, “P. & A. Kyriakou” Children's Hospital, Goudi, Athens, Greece
  12. 12Department of Pediatric Nephrology, Maria Fareri Children's Hospital, Westchester Medical Center, Valhalla, New York, USA
  13. 13Université Paris Descartes, Faculté de Médecine Paris Descartes, Paris, France
  1. Correspondence to Corinne Antignac, Inserm U983, 6e étage, Tour Lavoisier, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, Paris 75015, France; corinne.antignac{at}


Background Mutations in the PLCE1 gene encoding phospholipase C epsilon 1 (PLCɛ1) have been recently described in patients with early onset nephrotic syndrome (NS) and diffuse mesangial sclerosis (DMS). In addition, two cases of PLCE1 mutations associated with focal segmental glomerulosclerosis (FSGS) and later NS onset have been reported.

Method In order to better assess the spectrum of phenotypes associated with PLCE1 mutations, mutational analysis was performed in a worldwide cohort of 139 patients (95 familial cases belonging to 68 families and 44 sporadic cases) with steroid resistant NS presenting at a median age of 23.0 months (range 0–373).

Results Homozygous or compound heterozygous mutations were identified in 33% (8/24) of DMS cases. PLCE1 mutations were found in 8% (6/78) of FSGS cases without NPHS2 mutations. Nine were novel mutations. No clear genotype–phenotype correlation was observed, with either truncating or missense mutations detected in both DMS and FSGS, and leading to a similar renal evolution. Surprisingly, three unaffected and unrelated individuals were also found to carry the homozygous mutations identified in their respective families.

Conclusion PLCE1 is a major gene of DMS and is mutated in a non-negligible proportion of FSGS cases without NPHS2 mutations. Although additional variants in 19 candidate genes (16 other PLC genes, BRAF,IQGAP1 and NPHS1) were not identified, it is speculated that other modifier genes or environmental factors may play a role in the renal phenotype variability observed in individuals bearing PLCE1 mutations. This observation needs to be considered in the genetic counselling offered to patients.

  • PLCE1
  • nephrotic syndrome
  • diffuse mesangial sclerosis
  • focal segmental glomerulosclerosis
  • hereditary glomerular disease
  • molecular genetics
  • screening
  • renal medicine

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  • OB and GB contributed equally to this paper.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was approved by the Comité de Protection des Personnes «Ile de France II».

  • Provenance and peer review Not commissioned; externally peer reviewed.