Double homozygous missense mutations in DACH1 and BMP4 in a patient with bilateral cystic renal dysplasia.
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Double homozygous missense mutations in DACH1 and BMP4 in a patient with bilateral cystic renal dysplasia. / Schild, Raphael-Sebastian; Knüppel, Tanja; Konrad, Martin; Bergmann, Carsten; Trautmann, Agnes; Kemper, Markus J.; Wu, Kongming; Yaklichkin, Sergey; Wang, Jing; Pestell, Richard; Müller-Wiefel, Dirk E; Schaefer, Franz; Weber, Stefanie.
in: NEPHROL DIAL TRANSPL, Jahrgang 28, Nr. 1, 1, 2013, S. 227-232.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Double homozygous missense mutations in DACH1 and BMP4 in a patient with bilateral cystic renal dysplasia.
AU - Schild, Raphael-Sebastian
AU - Knüppel, Tanja
AU - Konrad, Martin
AU - Bergmann, Carsten
AU - Trautmann, Agnes
AU - Kemper, Markus J.
AU - Wu, Kongming
AU - Yaklichkin, Sergey
AU - Wang, Jing
AU - Pestell, Richard
AU - Müller-Wiefel, Dirk E
AU - Schaefer, Franz
AU - Weber, Stefanie
PY - 2013
Y1 - 2013
N2 - 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)-? 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-? 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.
AB - 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)-? 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-? 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.
KW - Adult
KW - Humans
KW - Male
KW - Young Adult
KW - Homozygote
KW - Mutation, Missense
KW - Genetic Association Studies
KW - Transcription Factors/genetics
KW - Eye Proteins/genetics
KW - Bone Morphogenetic Protein 4/genetics
KW - Kidney/abnormalities
KW - Polycystic Kidney, Autosomal Recessive/genetics
KW - Urogenital Abnormalities/genetics
KW - Adult
KW - Humans
KW - Male
KW - Young Adult
KW - Homozygote
KW - Mutation, Missense
KW - Genetic Association Studies
KW - Transcription Factors/genetics
KW - Eye Proteins/genetics
KW - Bone Morphogenetic Protein 4/genetics
KW - Kidney/abnormalities
KW - Polycystic Kidney, Autosomal Recessive/genetics
KW - Urogenital Abnormalities/genetics
M3 - SCORING: Journal article
VL - 28
SP - 227
EP - 232
JO - NEPHROL DIAL TRANSPL
JF - NEPHROL DIAL TRANSPL
SN - 0931-0509
IS - 1
M1 - 1
ER -
