title: Genetic screening in adolescents with steroid-resistant nephrotic syndrome.
abstract: Genetic screening paradigms for congenital and infantile nephrotic syndrome are well established; however, screening in adolescents has received only minor attention. To help rectify this, we analyzed an unselected adolescent cohort of the international PodoNet registry to develop a rational screening approach based on 227 patients with nonsyndromic steroid-resistant nephrotic syndrome aged 10-20 years. Of these, 21% had a positive family history. Autosomal dominant cases were screened for WT1, TRPC6, ACTN4, and INF2 mutations. All other patients had the NPHS2 gene screened, and WT1 was tested in sporadic cases. In addition, 40 sporadic cases had the entire coding region of INF2 tested. Of the autosomal recessive and the sporadic cases, 13 and 6%, respectively, were found to have podocin-associated nephrotic syndrome, and 56% of them were compound heterozygous for the nonneutral p.R229Q polymorphism. Four percent of the sporadic and 10% of the autosomal dominant cases had a mutation in WT1. Pathogenic INF2 mutations were found in 20% of the dominant but none of the sporadic cases. In a large cohort of adolescents including both familial and sporadic disease, NPHS2 mutations explained about 7% and WT1 4% of cases, whereas INF2 proved relevant only in autosomal dominant familial disease. Thus, screening of the entire coding sequence of NPHS2 and exons 8-9 of WT1 appears to be the most rational and cost-effective screening approach in sporadic juvenile steroid-resistant nephrotic syndrome.
authors.affiliation: Division of Pediatric Nephrology, Center for Pediatric and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany. b.lipska@gumed.edu.pl
authors.forename: Beata S
authors.initials: BS
authors.lastname: Lipska
authors.forename: Paraskevas
authors.initials: P
authors.lastname: Iatropoulos
authors.forename: Ramona
authors.initials: R
authors.lastname: Maranta
authors.forename: Gianluca
authors.initials: G
authors.lastname: Caridi
authors.forename: Fatih
authors.initials: F
authors.lastname: Ozaltin
authors.forename: Ali
authors.initials: A
authors.lastname: Anarat
authors.forename: Ayse
authors.initials: A
authors.lastname: Balat
authors.forename: Jutta
authors.initials: J
authors.lastname: Gellermann
authors.forename: Agnes
authors.initials: A
authors.lastname: Trautmann
authors.forename: Ozlem
authors.initials: O
authors.lastname: Erdogan
authors.forename: Bassam
authors.initials: B
authors.lastname: Saeed
authors.forename: Sevinc
authors.initials: S
authors.lastname: Emre
authors.forename: Radovan
authors.initials: R
authors.lastname: Bogdanovic
authors.forename: Marta
authors.initials: M
authors.lastname: Azocar
authors.forename: Irena
authors.initials: I
authors.lastname: Balasz-Chmielewska
authors.forename: Elisa
authors.initials: E
authors.lastname: Benetti
authors.forename: Salim
authors.initials: S
authors.lastname: Caliskan
authors.forename: Sevgi
authors.initials: S
authors.lastname: Mir
authors.forename: Anette
authors.initials: A
authors.lastname: Melk
authors.forename: Pelin
authors.initials: P
authors.lastname: Ertan
authors.forename: Esra
authors.initials: E
authors.lastname: Baskin
authors.forename: Helena
authors.initials: H
authors.lastname: Jardim
authors.forename: Tinatin
authors.initials: T
authors.lastname: Davitaia
authors.forename: Anna
authors.initials: A
authors.lastname: Wasilewska
authors.forename: Dorota
authors.initials: D
authors.lastname: Drozdz
authors.forename: Maria
authors.initials: M
authors.lastname: Szczepanska
authors.forename: Augustina
authors.initials: A
authors.lastname: Jankauskiene
authors.forename: Lina Maria Serna
authors.initials: LM
authors.lastname: Higuita
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Ardissino
authors.forename: Ozan
authors.initials: O
authors.lastname: Ozkaya
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Kuzma-Mroczkowska
authors.forename: Oguz
authors.initials: O
authors.lastname: Soylemezoglu
authors.forename: Bruno
authors.initials: B
authors.lastname: Ranchin
authors.forename: Anna
authors.initials: A
authors.lastname: Medynska
authors.forename: Marcin
authors.initials: M
authors.lastname: Tkaczyk
authors.forename: Amira
authors.initials: A
authors.lastname: Peco-Antic
authors.forename: Ipek
authors.initials: I
authors.lastname: Akil
authors.forename: Tomasz
authors.initials: T
authors.lastname: Jarmolinski
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Firszt-Adamczyk
authors.forename: Jiri
authors.initials: J
authors.lastname: Dusek
authors.forename: Giacomo D
authors.initials: GD
authors.lastname: Simonetti
authors.forename: Faysal
authors.initials: F
authors.lastname: Gok
authors.forename: Alaleh
authors.initials: A
authors.lastname: Gheissari
authors.forename: Francesco
authors.initials: F
authors.lastname: Emma
authors.forename: Rafael T
authors.initials: RT
authors.lastname: Krmar
authors.forename: Michel
authors.initials: M
authors.lastname: Fischbach
authors.forename: Nikoleta
authors.initials: N
authors.lastname: Printza
authors.forename: Eva
authors.initials: E
authors.lastname: Simkova
authors.forename: Caterina
authors.initials: C
authors.lastname: Mele
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Ghiggeri
authors.forename: Franz
authors.initials: F
authors.lastname: Schaefer
mesh_terms: D000185:Actinin / Q000235:genetics; D000293:Adolescent; D017668:Age of Onset; D002648:Child; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D000080865:Formins; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics; D009154:Mutation; D009404:Nephrotic Syndrome / Q000151:congenital* / Q000235:genetics / Q000628:therapy; D010375:Pedigree; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D012042:Registries; D050052:TRPC Cation Channels / Q000235:genetics; D000074287:TRPC6 Cation Channel; D025721:WT1 Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: C111453:ACTN4 protein, human; D000080865:Formins; C546959:INF2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; C407223:NPHS2 protein; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C117032:TRPC6 protein, human; D025721:WT1 Proteins; C583751:WT1 protein, human; D000185:Actinin