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

Autor:	Lipska-Ziętkiewicz BS; Department of Biology and Medical Genetics, Clinical Genetics Unit, Medical University of Gdansk, Gdansk, Poland., Gellermann J; Department of Pediatric Nephrology, Charité Universitätsmedizin Berlin, Charité Children's Hospital, Berlin, Germany., Boyer O; Inserm U1163, Imagine Institute, Paris Descartes University, Paris, France.; Pediatric Nephrology, Necker Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France., Gribouval O; Inserm U1163, Imagine Institute, Paris Descartes University, Paris, France., Ziętkiewicz S; Department of Molecular and Cellular Biology, Intercollegiate Faculty of Biotechnology, University of Gdańsk, Gdańsk, Poland., Kari JA; Pediatric Nephrology Center of Excellence, Pediatrics Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia., Shalaby MA; Pediatric Nephrology Center of Excellence, Pediatrics Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia., Ozaltin F; Nephrogenetics Laboratory, Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey.; Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey.; Hacettepe University Center for Biobanking and Genomics, Ankara, Turkey., Dusek J; Department of Pediatrics, University Hospital Motol, Prague, Czech Republic., Melk A; Pediatric Kidney, Liver and Metabolic Disease, MHH Children´s Hospital, Hannover, Germany., Bayazit AK; Department of Pediatric Nephrology, Cukurova University, Adana, Turkey., Massella L; Nephrology and Dialysis Unit, Pediatric Subspecialties Department, Bambino Gesú Children's Hospital, IRCCS, Rome, Italy., Hyla-Klekot L; Department of Pediatric Nephrology, Pediatrics and Oncology Center, Chorzów, Poland., Habbig S; Department of Pediatric Nephrology, University Children's Hospital Cologne, Germany., Godron A; Pediatric Nephrology Unit, Department of Pediatrics, Bordeaux University Hospital, Bordeaux, France., Szczepańska M; Chair and Department of Pediatrics, SMDZ in Zabrze, Medical University of Silesia in Katowice, Zabrze, Poland., Bieniaś B; Department of Pediatric Nephrology, Lublin Medical University, Lublin, Poland., Drożdż D; Department of Pediatric Nephrology and Hypertension, Dialysis Unit, Jagiellonian University Medical College, Krakow, Poland., Odeh R; Department of Pediatrics, School of Medicine, University of Jordan, Amman, Jordan., Jarmużek W; Department of Nephrology, Kidney Transplantation and Hypertension, The Children's Memorial Health Institute, Warsaw, Poland., Zachwieja K; Department of Pediatric Nephrology and Hypertension, Dialysis Unit, Jagiellonian University Medical College, Krakow, Poland., Trautmann A; Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany., Antignac C; Inserm U1163, Imagine Institute, Paris Descartes University, Paris, France.; Department of Genetics, Necker Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France., Schaefer F; Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany.
Jazyk:	angličtina
Zdroj:	PloS one [PLoS One] 2017 Aug 10; Vol. 12 (8), pp. e0180926. Date of Electronic Publication: 2017 Aug 10 (Print Publication: 2017).
DOI:	10.1371/journal.pone.0180926
Abstrakt:	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 oligosymptomatic 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.
Databáze:	MEDLINE
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