WNT3 involvement in human bladder exstrophy and cloaca development in zebrafish.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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WNT3 involvement in human bladder exstrophy and cloaca development in zebrafish. / Baranowska Körberg, Izabella; Hofmeister, Wolfgang; Markljung, Ellen; Cao, Jia; Nilsson, Daniel; Ludwig, Michael; Draaken, Markus; Holmdahl, Gundela; Barker, Gillian; Reutter, Heiko; Vukojević, Vladana; Clementson Kockum, Christina; Lundin, Johanna; Lindstrand, Anna; Nordenskjöld, Agneta.

I: Human Molecular Genetics, Vol. 24, Nr. 18, 2015, s. 5069-5078.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Baranowska Körberg, I, Hofmeister, W, Markljung, E, Cao, J, Nilsson, D, Ludwig, M, Draaken, M, Holmdahl, G, Barker, G, Reutter, H, Vukojević, V, Clementson Kockum, C, Lundin, J, Lindstrand, A & Nordenskjöld, A 2015, 'WNT3 involvement in human bladder exstrophy and cloaca development in zebrafish.', Human Molecular Genetics, vol. 24, nr. 18, s. 5069-5078. https://doi.org/10.1093/hmg/ddv225

APA

Baranowska Körberg, I., Hofmeister, W., Markljung, E., Cao, J., Nilsson, D., Ludwig, M., ... Nordenskjöld, A. (2015). WNT3 involvement in human bladder exstrophy and cloaca development in zebrafish. Human Molecular Genetics, 24(18), 5069-5078. https://doi.org/10.1093/hmg/ddv225

CBE

Baranowska Körberg I, Hofmeister W, Markljung E, Cao J, Nilsson D, Ludwig M, Draaken M, Holmdahl G, Barker G, Reutter H, Vukojević V, Clementson Kockum C, Lundin J, Lindstrand A, Nordenskjöld A. 2015. WNT3 involvement in human bladder exstrophy and cloaca development in zebrafish. Human Molecular Genetics. 24(18):5069-5078. https://doi.org/10.1093/hmg/ddv225

MLA

Vancouver

Baranowska Körberg I, Hofmeister W, Markljung E, Cao J, Nilsson D, Ludwig M et al. WNT3 involvement in human bladder exstrophy and cloaca development in zebrafish. Human Molecular Genetics. 2015;24(18):5069-5078. https://doi.org/10.1093/hmg/ddv225

Author

Baranowska Körberg, Izabella ; Hofmeister, Wolfgang ; Markljung, Ellen ; Cao, Jia ; Nilsson, Daniel ; Ludwig, Michael ; Draaken, Markus ; Holmdahl, Gundela ; Barker, Gillian ; Reutter, Heiko ; Vukojević, Vladana ; Clementson Kockum, Christina ; Lundin, Johanna ; Lindstrand, Anna ; Nordenskjöld, Agneta. / WNT3 involvement in human bladder exstrophy and cloaca development in zebrafish. I: Human Molecular Genetics. 2015 ; Vol. 24, Nr. 18. s. 5069-5078.

RIS

TY - JOUR

T1 - WNT3 involvement in human bladder exstrophy and cloaca development in zebrafish.

AU - Baranowska Körberg, Izabella

AU - Hofmeister, Wolfgang

AU - Markljung, Ellen

AU - Cao, Jia

AU - Nilsson, Daniel

AU - Ludwig, Michael

AU - Draaken, Markus

AU - Holmdahl, Gundela

AU - Barker, Gillian

AU - Reutter, Heiko

AU - Vukojević, Vladana

AU - Clementson Kockum, Christina

AU - Lundin, Johanna

AU - Lindstrand, Anna

AU - Nordenskjöld, Agneta

PY - 2015

Y1 - 2015

N2 - Bladder exstrophy, a severe congenital urological malformation when a child is born with an open urinary bladder, is the most common form of bladder exstrophy-epispadias complex (BEEC) with an incidence of 1:30.000 children of Caucasian descent. Recent studies suggest that WNT genes may contribute to the etiology of bladder exstrophy. Here, we evaluated WNT pathway genes in 20 bladder exstrophy patients using massively parallel sequencing. In total 13 variants were identified in WNT3, WNT6, WNT7A, WNT8B, WNT10A, WNT11, WNT16, FZD5, LRP1 and LRP10 genes and predicted as potentially disease causing, of which seven variants were novel. One variant, identified in a patient with a de novo nonsynonymous substitution in WNT3 (p.Cys91Arg), was further evaluated in zebrafish. Knock down of wnt3 in zebrafish showed cloaca malformations, including disorganization of the cloaca epithelium and expansion of the cloaca lumen. Our study suggests that the function of the WNT3 p.Cys91Arg variant was altered, since RNA overexpression of mutant Wnt3 RNA does not result in embryonic lethality as seen with wild type WNT3 mRNA. Finally, we also mutation screened the WNT3 gene further in 410 DNA samples from BEEC cases and identified one additional mutation c.638G>A (p.Gly213Asp), which was paternally inherited. In aggregate our data support the involvement of WNT pathway genes in BEEC and suggest that WNT3 in itself is a rare cause of BEEC.

AB - Bladder exstrophy, a severe congenital urological malformation when a child is born with an open urinary bladder, is the most common form of bladder exstrophy-epispadias complex (BEEC) with an incidence of 1:30.000 children of Caucasian descent. Recent studies suggest that WNT genes may contribute to the etiology of bladder exstrophy. Here, we evaluated WNT pathway genes in 20 bladder exstrophy patients using massively parallel sequencing. In total 13 variants were identified in WNT3, WNT6, WNT7A, WNT8B, WNT10A, WNT11, WNT16, FZD5, LRP1 and LRP10 genes and predicted as potentially disease causing, of which seven variants were novel. One variant, identified in a patient with a de novo nonsynonymous substitution in WNT3 (p.Cys91Arg), was further evaluated in zebrafish. Knock down of wnt3 in zebrafish showed cloaca malformations, including disorganization of the cloaca epithelium and expansion of the cloaca lumen. Our study suggests that the function of the WNT3 p.Cys91Arg variant was altered, since RNA overexpression of mutant Wnt3 RNA does not result in embryonic lethality as seen with wild type WNT3 mRNA. Finally, we also mutation screened the WNT3 gene further in 410 DNA samples from BEEC cases and identified one additional mutation c.638G>A (p.Gly213Asp), which was paternally inherited. In aggregate our data support the involvement of WNT pathway genes in BEEC and suggest that WNT3 in itself is a rare cause of BEEC.

U2 - 10.1093/hmg/ddv225

DO - 10.1093/hmg/ddv225

M3 - Article

VL - 24

SP - 5069

EP - 5078

JO - Human Molecular Genetics

T2 - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 18

ER -