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Targeted next-generation sequencing in steroid-resistant nephrotic syndrome : mutations in multiple glomerular genes may influence disease severity
Bullich Vilanova, Gemma (Institut d'Investigació Biomèdica Sant Pau)
Trujillano, Daniel (CIBER in Epidemiology and Public Health (CIBERESP))
Santín, Sheila (Institut d'Investigació Biomèdica Sant Pau)
Ossowski, Stephan (Genomic and Epigenomic Variation in Disease Group, Centre for Genomic Regulation (CRG))
Mendizábal, Santiago (Pediatric Nephrology Department, Hospital Universitario La Fe)
Fraga, Gloria (Pediatric Nephrology Department, Hospital de la Santa Creu i Sant Pau)
Madrid, Álvaro (Pediatric Nephrology Department, Hospital Vall d'Hebron)
Ariceta, Gema (Pediatric Nephrology Department, Hospital Vall d'Hebron)
Ballarín Castan, José Aurelio (Institut d'Investigació Biomèdica Sant Pau)
Torra Balcells, Roser (NInstitut d'Investigació Biomèdica Sant Pau)
Estivill, Xavier (CIBER in Epidemiology and Public Health (CIBERESP))
Ars Criach, Elisabet (Institut d'Investigació Biomèdica Sant Pau)
Instituto de Salud Carlos III

Date: 2014
Abstract: Genetic diagnosis of steroid-resistant nephrotic syndrome (SRNS) using Sanger sequencing is complicated by the high genetic heterogeneity and phenotypic variability of this disease. We aimed to improve the genetic diagnosis of SRNS by simultaneously sequencing 26 glomerular genes using massive parallel sequencing and to study whether mutations in multiple genes increase disease severity. High-throughput mutation analysis was performed in 50 SRNS and/or focal segmental glomerulosclerosis (FSGS) patients, a validation cohort of 25 patients with known pathogenic mutations, and a discovery cohort of 25 uncharacterized patients with probable genetic etiology. In the validation cohort, we identified the 42 previously known pathogenic mutations across NPHS1, NPHS2, WT1, TRPC6, and INF2 genes. In the discovery cohort, disease-causing mutations in SRNS/FSGS genes were found in nine patients. We detected three patients with mutations in an SRNS/FSGS gene and COL4A3. Two of them were familial cases and presented a more severe phenotype than family members with mutation in only one gene. In conclusion, our results show that massive parallel sequencing is feasible and robust for genetic diagnosis of SRNS/FSGS. Our results indicate that patients carrying mutations in an SRNS/FSGS gene and also in COL4A3 gene have increased disease severity.
Note: Número d'acord de subvenció SAF2008-00357
Note: Número d'acord de subvenció ISCIII/FIS/FEDER PI11/00733
Note: Número d'acord de subvenció EC/FP7/261123
Note: Número d'acord de subvenció EC/FP7/262055
Note: Número d'acord de subvenció FIS/12/01523
Note: Número d'acord de subvenció FIS/PI13/01731
Note: Número d'acord de subvenció ISCIII/RETIC/REDinREN/RD06/0016
Note: Número d'acord de subvenció ISCIII/RETIC/RD012/0021
Note: Número d'acord de subvenció AGAUR/2009/SGR-1116
Note: Altres ajuts:Fundación Renal Iñigo Álvarez de Toledo (FRIAT)
Rights: Tots els drets reservats
Language: Anglès.
Document: article ; recerca ; publishedVersion
Subject: Steroid-resistant nephrotic syndrome ; SRNS ; Genetic diagnosis ; Focal segmental glomerulosclerosis ; FSGS
Published in: European Journal of Human Genetics, Vol. 23 (november 2014) , p. 1192-1199, ISSN 1476-5438

DOI: 10.1038/ejhg.2014.252
PMID: 25407002


8 p, 444.5 KB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut d'Investigació Biomèdica Sant Pau
Articles > Research articles
Articles > Published articles

 Record created 2018-01-29, last modified 2019-02-07



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