Genetic diagnosis of steroid-resistant nephrotic syndrome in a longitudinal collection of Czech and Slovak patients: a high proportion of causative variants in NUP93

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F18%3A10376357" target="_blank" >RIV/00216208:11130/18:10376357 - isvavai.cz</a>

Alternative codes found

RIV/00064203:_____/18:10376357

Result on the web

<a href="https://doi.org/10.1007/s00467-018-3950-2" target="_blank" >https://doi.org/10.1007/s00467-018-3950-2</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00467-018-3950-2" target="_blank" >10.1007/s00467-018-3950-2</a>

Result language

angličtina

Original language name

Genetic diagnosis of steroid-resistant nephrotic syndrome in a longitudinal collection of Czech and Slovak patients: a high proportion of causative variants in NUP93

Original language description

Background: Steroid-resistant nephrotic syndrome (SRNS) has a heterogeneous spectrum of monogenic causes that substantially differ among populations. The aim of this study was to analyse the genetic aetiology of SRNS in Czech and Slovak paediatric patients. Methods: We analysed clinical data from 74 patients (38 boys) with congenital (15%), infant (14%), and childhood-onset (71%) SRNS collected from the Czech Republic and Slovakia from 2000 to 2017 (inclusive). The DNA samples were first analysed by Sanger sequencing (genes NPHS2, NPHS1, and WT1) and then by next generation sequencing (NGS) using a targeted panel of 48 genes previously associated with SRNS. Family segregation of the causative variants was confirmed by Sanger sequencing when possible. Results: Genetic diagnosis was established in 28/74 patients (38%) based on findings of pathogenic or likely pathogenic causative variants in genotypes conforming to the expected mode of inheritance. Sanger sequencing diagnosed 26% of patients, whereas second-tier testing by a targeted NGS panel diagnosed a further 12%. Frequent causative genes were NPHS2 (15%), WT1 (9.5%), and surprisingly NUP93 with four (5.4%) unrelated cases. Additional causative genes included COQ2 (two patients), NPHS1, INF2, DGKE, and LMX1B (one patient each). Conclusions: Compared with outright use of NGS, our tiered genetic testing strategy was considerably more rapid and marginally less expensive. Apart from a high aetiological fraction of NPHS2 and WT1 genes, our study has identified an unexpectedly high frequency of a limited set of presumably ancestral causative mutations in NUP93. The results may aid in tailoring testing strategies in Central European populations.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30217 - Urology and nephrology

Project

<a href="/en/project/NV15-31586A" target="_blank" >NV15-31586A: Individualization of therapy of rare nephropathies in children based on new molecular pathophysiology diagnostic</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Pediatric Nephrology

ISSN

0931-041X

e-ISSN

—

Volume of the periodical

33

Issue of the periodical within the volume

8

Country of publishing house

DE - GERMANY

Number of pages

17

Pages from-to

1347-1363

UT code for WoS article

000436405900009

EID of the result in the Scopus database

2-s2.0-85048019754