Okorn, Christine, Goertz, Anne, Vester, Udo, Beck, Bodo B., Bergmann, Carsten, Habbig, Sandra, Koenig, Jens, Konrad, Martin, Mueller, Dominik, Oh, Jun, Ortiz-Bruechle, Nadina, Patzer, Ludwig, Schild, Raphael, Seeman, Tomas, Staudeu, Hagen, Thumfart, Julia ORCID: 0000-0003-1162-5295, Toenshoff, Burkhard, Walden, Ulrike, Weber, Lutz, Zaniew, Marcin, Zappel, Hildegard, Hoyer, Peter F. and Weber, Stefanie (2019). HNF1B nephropathy has a slow-progressive phenotype in childhood-with the exception of very early onset cases: results of the German Multicenter HNF1B Childhood Registry. Pediatr. Nephrol., 34 (6). S. 1065 - 1076. NEW YORK: SPRINGER. ISSN 1432-198X

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Abstract

Background HNF1B gene mutations are an important cause of bilateral (cystic) dysplasia in children, complicated by chronic renal insufficiency. The clinical variability, the absence of genotype-phenotype correlations, and limited long-term data render counseling of affected families difficult. Methods Longitudinal data of 62 children probands with genetically proven HNF1B nephropathy was obtained in a multicenter approach. Genetic family cascade screening was performed in 30/62 cases. Results Eighty-seven percent of patients had bilateral dysplasia, 74% visible bilateral, and 16% unilateral renal cysts at the end of observation. Cyst development was non-progressive in 72% with a mean glomerular filtration rate (GFR) loss of -0.33 ml/min/1.73m(2) per year (8.9). In patients with an increase in cyst number, the annual GFR reduction was -2.8 ml/min/1.73m(2) (+/- 13.2), in the total cohort -1.0 ml/min/1.73m(2) (+/- 10.3). A subset of HNF1B patients differs from this group and develops end stage renal disease (ESRD) at very early ages < 2 years. Hyperuricemia (37%) was a frequent finding at young age (median 1 year), whereas hypomagnesemia (24%), elevated liver enzymes (21%), and hyperglycemia (8%) showed an increased incidence in the teenaged child. Genetic analysis revealed no genotype-phenotype correlations but a significant parent-of-origin effect with a preponderance of 81% of maternal inheritance in dominant cases. Conclusions In most children, HNF1B nephropathy has a non-progressive course of cyst development and a slow-progressive course of kidney function. A subgroup of patients developed ESRD at very young age < 2 years requiring special medical attention. The parent-of-origin effect suggests an influence of epigenetic modifiers in HNF1B disease.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Okorn, ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goertz, AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vester, UdoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beck, Bodo B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bergmann, CarstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Habbig, SandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koenig, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Konrad, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, DominikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oh, JunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ortiz-Bruechle, NadinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Patzer, LudwigUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schild, RaphaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seeman, TomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Staudeu, HagenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thumfart, JuliaUNSPECIFIEDorcid.org/0000-0003-1162-5295UNSPECIFIED
Toenshoff, BurkhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Walden, UlrikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weber, LutzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zaniew, MarcinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zappel, HildegardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoyer, Peter F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weber, StefanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-147427
DOI: 10.1007/s00467-018-4188-8
Journal or Publication Title: Pediatr. Nephrol.
Volume: 34
Number: 6
Page Range: S. 1065 - 1076
Date: 2019
Publisher: SPRINGER
Place of Publication: NEW YORK
ISSN: 1432-198X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
HEPATOCYTE NUCLEAR FACTOR-1-BETA; LONG-TERM PROGNOSIS; 201 ADULT PATIENTS; CLINICAL SPECTRUM; GENOTYPE/PHENOTYPE CORRELATIONS; RENAL DYSPLASIA; KIDNEY-DISEASE; GENE TCF2; MUTATIONS; CHILDRENMultiple languages
Pediatrics; Urology & NephrologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/14742

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