Low renal but high extrarenal phenotype variability in Schimke immuno-osseous dysplasia

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F17%3A10373769" target="_blank" >RIV/00216208:11130/17:10373769 - isvavai.cz</a>

Alternative codes found

RIV/00064203:_____/17:10373769

Result on the web

<a href="https://doi.org/10.1371/journal.pone.0180926" target="_blank" >https://doi.org/10.1371/journal.pone.0180926</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1371/journal.pone.0180926" target="_blank" >10.1371/journal.pone.0180926</a>

Result language

angličtina

Original language name

Low renal but high extrarenal phenotype variability in Schimke immuno-osseous dysplasia

Original language description

Schimke immuno-osseous dysplasia (SIOD) is a rare multisystem disorder with early mortality and steroid-resistant nephrotic syndrome (SRNS) progressing to end-stage kidney disease. We hypothesized that next-generation gene panel sequencing may unsurface oli-gosymptomatic cases of SIOD with potentially milder disease courses. We analyzed the renal and extrarenal phenotypic spectrum and genotype-phenotype associations in 34 patients from 28 families, the largest SMARCAL1-associated nephropathy cohort to date. In 11 patients the diagnosis was made unsuspectedly through SRNS gene panel testing. Renal disease first manifested at median age 4.5 yrs, with focal segmental glmerulosclerosis or minimal change nephropathy on biopsy and rapid progression to end-stage kidney disease (ESKD) at median age 8.7 yrs. Whereas patients diagnosed by phenotype more frequently developed severe extrarenal complications (cerebral ischemic events, septicemia) and were more likely to die before age 10 years than patients identified by SRNS-gene panel screening (88 vs. 40%), the subgroups did not differ with respect to age at proteinuria onset and progression to ESKD. Also, 10 of 11 children diagnosed unsuspectedly by Next Generation Sequencing were small at diagnosis and all showed progressive growth failure. Severe phenotypes were usually associated with biallelic truncating mutations and milder phenotypes with biallelic missense mutations. However, no genotype-phenotype correlation was observed for the renal disease course. In conclusion, while short stature is a reliable clue to SIOD in children with SRNS, other systemic features are highly variable. Our findings support routine SMARCAL1 testing also in non-syndromic SRNS.

Czech name

—

Czech description

—

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

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

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

Name of the periodical

PLoS One

ISSN

1932-6203

e-ISSN

—

Volume of the periodical

12

Issue of the periodical within the volume

8

Country of publishing house

US - UNITED STATES

Number of pages

12

Pages from-to

—

UT code for WoS article

000407396200010

EID of the result in the Scopus database

2-s2.0-85027219757