BACKGROUND: The most frequently mutated gene of steroid-resistant nephrotic syndrome (SRNS) is NPHS2. Current guidelines propose the sequencing of all NPHS2 exons only in childhood-onset SRNS. METHODS: A cohort of 38 Hungarian patients with childhood-onset nephrotic-range proteinuria was screened for NPHS2 mutations. The frequency of the p.V290M mutation in late-onset SRNS was examined in the French and PodoNet cohorts. RESULTS: Of the 38 Hungarian patients screened, seven carried NPHS2 mutations on both alleles, of whom two-diagnosed with proteinuria through school screening programs at the age of 9.7 and 14 years, respectively-did not develop nephrotic syndrome in childhood. The first, an 18-year-old boy, homozygous for p.V290M, has never developed edema. The second, a 31-year-old woman-compound heterozygous for p.V290M and p.R138Q-was first detected with hypoalbuminemia (<30 g/l) and edema at the age of 24.3 and 27.5 years, respectively. Both patients currently have a normal glomerular filtration rate. The mutation p.V290M was carried by three of the 38 patients in the Hungarian cohort, by two of the 95 patients with late-onset SRNS in the PodoNet cohort and by none of the 83 patients in the French cohort. CONCLUSIONS: We propose that not only the p.R229Q variant, but also the p.V290M mutation should be screened in Central and Eastern European patients with late-onset SRNS.
BACKGROUND: The most frequently mutated gene of steroid-resistant nephrotic syndrome (SRNS) is NPHS2. Current guidelines propose the sequencing of all NPHS2 exons only in childhood-onset SRNS. METHODS: A cohort of 38 Hungarian patients with childhood-onset nephrotic-range proteinuria was screened for NPHS2 mutations. The frequency of the p.V290M mutation in late-onset SRNS was examined in the French and PodoNet cohorts. RESULTS: Of the 38 Hungarian patients screened, seven carried NPHS2 mutations on both alleles, of whom two-diagnosed with proteinuria through school screening programs at the age of 9.7 and 14 years, respectively-did not develop nephrotic syndrome in childhood. The first, an 18-year-old boy, homozygous for p.V290M, has never developed edema. The second, a 31-year-old woman-compound heterozygous for p.V290M and p.R138Q-was first detected with hypoalbuminemia (<30 g/l) and edema at the age of 24.3 and 27.5 years, respectively. Both patients currently have a normal glomerular filtration rate. The mutation p.V290M was carried by three of the 38 patients in the Hungarian cohort, by two of the 95 patients with late-onset SRNS in the PodoNet cohort and by none of the 83 patients in the French cohort. CONCLUSIONS: We propose that not only the p.R229Q variant, but also the p.V290M mutation should be screened in Central and Eastern European patients with late-onset SRNS.
Authors: J M Kaplan; S H Kim; K N North; H Rennke; L A Correia; H Q Tong; B J Mathis; J C Rodríguez-Pérez; P G Allen; A H Beggs; M R Pollak Journal: Nat Genet Date: 2000-03 Impact factor: 38.330
Authors: N Boute; O Gribouval; S Roselli; F Benessy; H Lee; A Fuchshuber; K Dahan; M C Gubler; P Niaudet; C Antignac Journal: Nat Genet Date: 2000-04 Impact factor: 38.330
Authors: Rainer G Ruf; Anne Lichtenberger; Stephanie M Karle; Johannes P Haas; Franzisco E Anacleto; Michael Schultheiss; Isabella Zalewski; Anita Imm; Eva-Maria Ruf; Bettina Mucha; Arvind Bagga; Thomas Neuhaus; Arno Fuchshuber; Aysin Bakkaloglu; Friedhelm Hildebrandt Journal: J Am Soc Nephrol Date: 2004-03 Impact factor: 10.121
Authors: M Kestilä; U Lenkkeri; M Männikkö; J Lamerdin; P McCready; H Putaala; V Ruotsalainen; T Morita; M Nissinen; R Herva; C E Kashtan; L Peltonen; C Holmberg; A Olsen; K Tryggvason Journal: Mol Cell Date: 1998-03 Impact factor: 17.970
Authors: Elizabeth J Brown; Johannes S Schlöndorff; Daniel J Becker; Hiroyasu Tsukaguchi; Stephen J Tonna; Andrea L Uscinski; Henry N Higgs; Joel M Henderson; Martin R Pollak Journal: Nat Genet Date: 2009-12-20 Impact factor: 38.330
Authors: Ethan S Sen; Philip Dean; Laura Yarram-Smith; Agnieszka Bierzynska; Geoff Woodward; Chris Buxton; Gemma Dennis; Gavin I Welsh; Maggie Williams; Moin A Saleem Journal: J Med Genet Date: 2017-08-05 Impact factor: 6.318
Authors: Beata S Lipska; Irena Balasz-Chmielewska; Lucyna Morzuch; Kacper Wasielewski; Dominika Vetter; Halina Borzecka; Dorota Drozdz; Agnieszka Firszt-Adamczyk; Ewa Gacka; Tomasz Jarmolinski; Joanna Ksiazek; Elzbieta Kuzma-Mroczkowska; Mieczyslaw Litwin; Anna Medynska; Magdalena Silska; Maria Szczepanska; Marcin Tkaczyk; Anna Wasilewska; Franz Schaefer; Aleksandra Zurowska; Janusz Limon Journal: J Appl Genet Date: 2013-05-05 Impact factor: 3.240