Universität zu Köln

Lipska-Zietkiewicz, Beata S. ORCID: 0000-0002-4169-9685, Gellermann, Jutta, Boyer, Olivia ORCID: 0000-0002-3957-1359, Gribouval, Olivier ORCID: 0000-0003-0238-8224, Zietkiewicz, Szymon ORCID: 0000-0002-3435-4603, Kari, Jameela A., Shalaby, Mohamed A., Ozaltin, Fatih, Dusek, Jiri, Melk, Anette, Bayazit, Aysun K., Massella, Laura, Hyla-Klekot, Lidia, Habbig, Sandra, Godron, Astrid, Szczepanska, Maria ORCID: 0000-0002-6772-1983, Bienias, Beata ORCID: 0000-0002-0176-9845, Drozdz, Dorota, Odeh, Rasha ORCID: 0000-0002-8419-0547, Jarmuzek, Wioletta ORCID: 0000-0002-9929-7486, Zachwieja, Katarzyna, Trautmann, Agnes, Antignac, Corinne and Schaefer, Franz (2017). Low renal but high extrarenal phenotype variability in Schimke immuno-osseous dysplasia. PLoS One, 12 (8). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lipska-Zietkiewicz, Beata S. UNSPECIFIED orcid.org/0000-0002-4169-9685 UNSPECIFIED Gellermann, Jutta UNSPECIFIED UNSPECIFIED UNSPECIFIED Boyer, Olivia UNSPECIFIED orcid.org/0000-0002-3957-1359 UNSPECIFIED Gribouval, Olivier UNSPECIFIED orcid.org/0000-0003-0238-8224 UNSPECIFIED Zietkiewicz, Szymon UNSPECIFIED orcid.org/0000-0002-3435-4603 UNSPECIFIED Kari, Jameela A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Shalaby, Mohamed A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ozaltin, Fatih UNSPECIFIED UNSPECIFIED UNSPECIFIED Dusek, Jiri UNSPECIFIED UNSPECIFIED UNSPECIFIED Melk, Anette UNSPECIFIED UNSPECIFIED UNSPECIFIED Bayazit, Aysun K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Massella, Laura UNSPECIFIED UNSPECIFIED UNSPECIFIED Hyla-Klekot, Lidia UNSPECIFIED UNSPECIFIED UNSPECIFIED Habbig, Sandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Godron, Astrid UNSPECIFIED UNSPECIFIED UNSPECIFIED Szczepanska, Maria UNSPECIFIED orcid.org/0000-0002-6772-1983 UNSPECIFIED Bienias, Beata UNSPECIFIED orcid.org/0000-0002-0176-9845 UNSPECIFIED Drozdz, Dorota UNSPECIFIED UNSPECIFIED UNSPECIFIED Odeh, Rasha UNSPECIFIED orcid.org/0000-0002-8419-0547 UNSPECIFIED Jarmuzek, Wioletta UNSPECIFIED orcid.org/0000-0002-9929-7486 UNSPECIFIED Zachwieja, Katarzyna UNSPECIFIED UNSPECIFIED UNSPECIFIED Trautmann, Agnes UNSPECIFIED UNSPECIFIED UNSPECIFIED Antignac, Corinne UNSPECIFIED UNSPECIFIED UNSPECIFIED Schaefer, Franz UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-221821
DOI:	10.1371/journal.pone.0180926
Journal or Publication Title:	PLoS One
Volume:	12
Number:	8
Date:	2017
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NEPHROTIC SYNDROME; STEROID-RESISTANT; EXPRESSION Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22182