BACKGROUND AND AIMS: Several genes have been identified to be causative for the disease in a subset of patients with focal segmental glomerulosclerosis (FSGS) and nephrotic syndrome (NS). Mutations in genes with autosomal dominant inheritance mostly affect adolescent or adult patients. In rare cases recessive mutations in NPHS2 are associated with late-onset FSGS. Hereditary FSGS is associated with poor renal survival and low rates of disease recurrence after renal transplantation. Aim of the study was to evaluate the incidence of gene mutations within a cohort of adult patients with primary FSGS and/or NS and progression to end-stage renal disease (ESRD). METHODS: Genotyping for TRPC6, ACTN4, CD2AP, WT1, INF2, NPHS2 and NPHS1 was performed in all patients with primary FSGS and ESRD registered on the waiting list for kidney transplantation of a large German transplant center (n = 26 out of 478 registered patients). Mean age at onset was 31.7 years; a positive family history for renal disease was documented in 11 (42%) patients, of these one with familiar history of FSGS. RESULTS: A missense mutation (p.R360H) was identified in TRPC6, 2 missense mutations in compound heterozygous state in NPHS1 (p.P368L; p.G412C), a sequence variation of unknown significance (p.R310Q) in ACTN4 and the non-neutral NPHS2 polymorphism p.R229Q in two additional patients. No mutations were detected in INF2, CD2AP and WT1. CONCLUSIONS: The observed mutation rate was 8% in this single-center cohort of adult patients with primary FSGS. Mutations in podocyte genes seem to be a rare cause of FSGS and renal failure in adult patients. However, they should be considered as the underlying cause in a subset of patient as the impact on family counseling and patients' life perspectives are significant.
BACKGROUND AND AIMS: Several genes have been identified to be causative for the disease in a subset of patients with focal segmental glomerulosclerosis (FSGS) and nephrotic syndrome (NS). Mutations in genes with autosomal dominant inheritance mostly affect adolescent or adult patients. In rare cases recessive mutations in NPHS2 are associated with late-onset FSGS. Hereditary FSGS is associated with poor renal survival and low rates of disease recurrence after renal transplantation. Aim of the study was to evaluate the incidence of gene mutations within a cohort of adult patients with primary FSGS and/or NS and progression to end-stage renal disease (ESRD). METHODS: Genotyping for TRPC6, ACTN4, CD2AP, WT1, INF2, NPHS2 and NPHS1 was performed in all patients with primary FSGS and ESRD registered on the waiting list for kidney transplantation of a large German transplant center (n = 26 out of 478 registered patients). Mean age at onset was 31.7 years; a positive family history for renal disease was documented in 11 (42%) patients, of these one with familiar history of FSGS. RESULTS: A missense mutation (p.R360H) was identified in TRPC6, 2 missense mutations in compound heterozygous state in NPHS1 (p.P368L; p.G412C), a sequence variation of unknown significance (p.R310Q) in ACTN4 and the non-neutral NPHS2 polymorphism p.R229Q in two additional patients. No mutations were detected in INF2, CD2AP and WT1. CONCLUSIONS: The observed mutation rate was 8% in this single-center cohort of adult patients with primary FSGS. Mutations in podocyte genes seem to be a rare cause of FSGS and renal failure in adult patients. However, they should be considered as the underlying cause in a subset of patient as the impact on family counseling and patients' life perspectives are significant.
Authors: An S De Vriese; Sanjeev Sethi; Karl A Nath; Richard J Glassock; Fernando C Fervenza Journal: J Am Soc Nephrol Date: 2018-01-10 Impact factor: 10.121
Authors: Rasheed A Gbadegesin; Gentzon Hall; Adebowale Adeyemo; Nils Hanke; Irini Tossidou; James Burchette; Guanghong Wu; Alison Homstad; Matthew A Sparks; Jose Gomez; Ruiji Jiang; Andrea Alonso; Peter Lavin; Peter Conlon; Ron Korstanje; M Christine Stander; Ghaidan Shamsan; Moumita Barua; Robert Spurney; Pravin C Singhal; Jeffrey B Kopp; Hermann Haller; David Howell; Martin R Pollak; Andrey S Shaw; Mario Schiffer; Michelle P Winn Journal: J Am Soc Nephrol Date: 2014-03-27 Impact factor: 10.121
Authors: Marc Riehle; Anja K Büscher; Björn-Oliver Gohlke; Mario Kaßmann; Maria Kolatsi-Joannou; Jan H Bräsen; Mato Nagel; Jan U Becker; Paul Winyard; Peter F Hoyer; Robert Preissner; Dietmar Krautwurst; Maik Gollasch; Stefanie Weber; Christian Harteneck Journal: J Am Soc Nephrol Date: 2016-02-18 Impact factor: 10.121