Novel NPHS2 variant in patients with familial steroid-resistant nephrotic syndrome with early onset, slow progression and dominant inheritance pattern

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Suvanto , M , Patrakka , J , Jahnukainen , T , Sjostrom , P-M , Nuutinen , M , Arikoski , P , Kataja , J , Kestila , M & Jalanko , H 2017 , ' Novel NPHS2 variant in patients with familial steroid-resistant nephrotic syndrome with early onset, slow progression and dominant inheritance pattern ' , Clinical and Experimental Nephrology , vol. 21 , no. 4 , pp. 677-684 . https://doi.org/10.1007/s10157-016-1331-3

Title: Novel NPHS2 variant in patients with familial steroid-resistant nephrotic syndrome with early onset, slow progression and dominant inheritance pattern
Author: Suvanto, Maija; Patrakka, Jaakko; Jahnukainen, Timo; Sjostrom, Pia-Maria; Nuutinen, Matti; Arikoski, Pekka; Kataja, Janne; Kestila, Marjo; Jalanko, Hannu
Contributor: University of Helsinki, Children's Hospital
University of Helsinki, Children's Hospital
University of Helsinki, Children's Hospital
Date: 2017-08
Language: eng
Number of pages: 8
Belongs to series: Clinical and Experimental Nephrology
ISSN: 1342-1751
URI: http://hdl.handle.net/10138/238191
Abstract: Background Steroid-resistant nephrotic syndrome (SRNS) is a common cause of end-stage renal disease in children but also occurs as an adult-onset condition. In a subset of SRNS patients, pathogenic variants are found in genes coding for podocyte foot process proteins. The aim of this study was to define the role of pathogenic variants in Finnish patients with familial and sporadic SRNS. Methods We analyzed SRNS-related genes NPHS1, NPHS2, NEPH1, ACTN4, TRPC6, INF2, WT1, CD2AP, LAMB2, and PLCE1 for disease-causing variants using direct sequencing of exons and intron/exon boundaries in all members of a family with dominant SRNS with early onset and slow progression to end-stage renal disease. We carried out a whole genome sequencing in two affected and two healthy family members. The function of found podocin variant was studied using co-immunoprecipitation and immunohistochemistry. Podocyte gene sequences were analyzed in a cohort of Finnish non-familial SRNS patients. Results A heterozygous de novo deletion, c. 988_989delCT in NPHS2, was found in all affected family members and in none of their healthy relatives, non-familial patients or controls. No other SRNS-related gene variant, coding or non-coding co-segregated with the disease phenotype in the family. While the truncated podocin remained able to bind nephrin, the expression of nephrin was fragmented and podocin expression reduced. The gene analysis of the non-familial SRNS patients revealed few variants. Conclusion The role of podocin variants in nephrotic syndrome may be more varied than previously thought.
Subject: Podocin
Podocyte
Glomerulus
FOCAL SEGMENTAL GLOMERULOSCLEROSIS
MUTATIONS
NEPHRIN
PROTEIN
GENE
PODOCYTES
CHILDREN
PODOCIN
R229Q
3121 General medicine, internal medicine and other clinical medicine
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