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Double homozygous missense mutations in DACH1 and BMP4 in a patient with bilateral cystic renal dysplasia

Renal hypodysplasia (RHD) is characterized by small and/or disorganized kidneys following abnormal organogenesis. Mutations in several genes have been identified recently to be associated with RHD in humans, including BMP4, a member of the transforming growth factor (TGF)-β family of growth factors....

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Main Authors: Schild, Raphael-Sebastian (Author) , Knüppel, Tanja (Author) , Konrad, Martin (Author) , Bergmann, Carsten (Author) , Trautmann, Agnes (Author) , Kemper, Markus J. (Author) , Wu, Kongming (Author) , Yaklichkin, Sergey (Author) , Wang, Jing (Author) , Pestell, Richard (Author) , Müller-Wiefel, Dirk E. (Author) , Schaefer, Franz (Author) , Weber, Stefanie (Author)
Format: Article (Journal)
Language:English
Published: 2013
In: Nephrology, dialysis, transplantation
Year: 2013, Volume: 28, Issue: 1, Pages: 227-232
ISSN:1460-2385
DOI:10.1093/ndt/gfs539
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/ndt/gfs539
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Author Notes:Raphael Schild, Tanja Knüppel, Martin Konrad, Carsten Bergmann, Agnes Trautmann, Markus J. Kemper, Kongming Wu, Sergey Yaklichkin, Jing Wang, Richard Pestell, Dirk E. Müller-Wiefel, Franz Schaefer and Stefanie Weber
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Summary:Renal hypodysplasia (RHD) is characterized by small and/or disorganized kidneys following abnormal organogenesis. Mutations in several genes have been identified recently to be associated with RHD in humans, including BMP4, a member of the transforming growth factor (TGF)-β family of growth factors. DACH1 has been proposed as a candidate gene for RHD because of its involvement in the EYA-SIX-DACH network of renal developmental genes. Here, we present a patient with renal dysplasia carrying homozygous missense mutations in both BMP4 (p.N150K) and DACH1 (p.R684C). The genotype-phenotype correlation in the family hints at an oligogenic mode of inheritance of the disease in this kindred. Functional analyses of the identified DACH1 mutation in HEK293T cells demonstrated enhanced suppression of the TGF-β pathway suggesting that both mutations could act synergistically in the development of the phenotype in this patient. This finding provides a model for RHD as an oligo-/polygenic disorder and supports a role for DACH1 in the development of RHD in humans.
Item Description:Advance access publication 21 December 2012
Gesehen am 24.06.2021
Physical Description:Online Resource
ISSN:1460-2385
DOI:10.1093/ndt/gfs539

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