Muscarinic acetylcholine receptor m3 mutation causes urinary bladder disease and a prune-belly-like syndrome

Stefanie Weber; Holger Thiele; Sevgi Mir; Mohammad Reza Toliat; Betül Sozeri; Heiko Reutter; Markus Draaken; Michael Ludwig; Janine Altmüller; Peter Frommolt; Helen M. Stuart; Parisa Ranjzad; Neil A. Hanley; Rachel Jennings; William G. Newman; Duncan T. Wilcox; Uwe Thiel; Karl Peter Schlingmann; Rolf Beetz; Peter F. Hoyer; Martin Konrad; Franz Schaefer; Peter Nürnberg; Adrian S. Woolf

doi:10.1016/j.ajhg.2011.10.007

Muscarinic acetylcholine receptor m3 mutation causes urinary bladder disease and a prune-belly-like syndrome

Stefanie Weber^*, Holger Thiele, Sevgi Mir, Mohammad Reza Toliat, Betül Sozeri, Heiko Reutter, Markus Draaken, Michael Ludwig, Janine Altmüller, Peter Frommolt, Helen M. Stuart, Parisa Ranjzad, Neil A. Hanley, Rachel Jennings, William G. Newman, Duncan T. Wilcox, Uwe Thiel, Karl Peter Schlingmann, Rolf Beetz, Peter F. HoyerMartin Konrad, Franz Schaefer, Peter Nürnberg, Adrian S. Woolf

^*Corresponding author for this work

Medicine and Health

Research output: Contribution to journal › Article › peer-review

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Abstract

Urinary bladder malformations associated with bladder outlet obstruction are a frequent cause of progressive renal failure in children. We here describe a muscarinic acetylcholine receptor M3 (CHRM3) (1q41-q44) homozygous frameshift mutation in familial congenital bladder malformation associated with a prune-belly-like syndrome, defining an isolated gene defect underlying this sometimes devastating disease. CHRM3 encodes the M3 muscarinic acetylcholine receptor, which we show is present in developing renal epithelia and bladder muscle. These observations may imply that M3 has a role beyond its known contribution to detrusor contractions. This Mendelian disease caused by a muscarinic acetylcholine receptor mutation strikingly phenocopies Chrm3 null mutant mice.

Original language	English
Pages (from-to)	668-674
Number of pages	7
Journal	American Journal of Human Genetics
Volume	89
Issue number	5
DOIs	https://doi.org/10.1016/j.ajhg.2011.10.007
Publication status	Published - 11 Nov 2011

Bibliographical note

Funding Information:
We thank the patients and their family for participating in this study, Bettina Cirkel and Christian Becker for excellent technical support and Anne Deix for critical advice. Financial grant support was received from the Kidney Research UK (W.G.N. and A.S.W.), Kids Kidney Research and Kidneys for Life (A.S.W.), Manchester NIHR Biomedical Research Centre (A.S.W., R.J., N.A.H., H.S., and W.G.N.), and The Wellcome Trust (A.S.W. and N.A.H.). S.W. and F.S. received financial support from the Fritz Thyssen grant. H.R. and M.D. are members of the German network for congenital uro-rectal malformations (CURE-Net), which is supported by a research grant (01GM08107) from the German Federal Ministry of Education and Research. The 4C-Kidney Disease Study is supported by research grants of the KfH Foundation for Preventive Medicine, ERA-EDTA and IFB Transplantation.

ASJC Scopus subject areas

Genetics
Genetics(clinical)

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10.1016/j.ajhg.2011.10.007

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Weber, S., Thiele, H., Mir, S., Toliat, M. R., Sozeri, B., Reutter, H., Draaken, M., Ludwig, M., Altmüller, J., Frommolt, P., Stuart, H. M., Ranjzad, P., Hanley, N. A., Jennings, R., Newman, W. G., Wilcox, D. T., Thiel, U., Schlingmann, K. P., Beetz, R., ... Woolf, A. S. (2011). Muscarinic acetylcholine receptor m3 mutation causes urinary bladder disease and a prune-belly-like syndrome. American Journal of Human Genetics, 89(5), 668-674. https://doi.org/10.1016/j.ajhg.2011.10.007

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title = "Muscarinic acetylcholine receptor m3 mutation causes urinary bladder disease and a prune-belly-like syndrome",

abstract = "Urinary bladder malformations associated with bladder outlet obstruction are a frequent cause of progressive renal failure in children. We here describe a muscarinic acetylcholine receptor M3 (CHRM3) (1q41-q44) homozygous frameshift mutation in familial congenital bladder malformation associated with a prune-belly-like syndrome, defining an isolated gene defect underlying this sometimes devastating disease. CHRM3 encodes the M3 muscarinic acetylcholine receptor, which we show is present in developing renal epithelia and bladder muscle. These observations may imply that M3 has a role beyond its known contribution to detrusor contractions. This Mendelian disease caused by a muscarinic acetylcholine receptor mutation strikingly phenocopies Chrm3 null mutant mice.",

author = "Stefanie Weber and Holger Thiele and Sevgi Mir and Toliat, {Mohammad Reza} and Bet{\"u}l Sozeri and Heiko Reutter and Markus Draaken and Michael Ludwig and Janine Altm{\"u}ller and Peter Frommolt and Stuart, {Helen M.} and Parisa Ranjzad and Hanley, {Neil A.} and Rachel Jennings and Newman, {William G.} and Wilcox, {Duncan T.} and Uwe Thiel and Schlingmann, {Karl Peter} and Rolf Beetz and Hoyer, {Peter F.} and Martin Konrad and Franz Schaefer and Peter N{\"u}rnberg and Woolf, {Adrian S.}",

note = "Funding Information: We thank the patients and their family for participating in this study, Bettina Cirkel and Christian Becker for excellent technical support and Anne Deix for critical advice. Financial grant support was received from the Kidney Research UK (W.G.N. and A.S.W.), Kids Kidney Research and Kidneys for Life (A.S.W.), Manchester NIHR Biomedical Research Centre (A.S.W., R.J., N.A.H., H.S., and W.G.N.), and The Wellcome Trust (A.S.W. and N.A.H.). S.W. and F.S. received financial support from the Fritz Thyssen grant. H.R. and M.D. are members of the German network for congenital uro-rectal malformations (CURE-Net), which is supported by a research grant (01GM08107) from the German Federal Ministry of Education and Research. The 4C-Kidney Disease Study is supported by research grants of the KfH Foundation for Preventive Medicine, ERA-EDTA and IFB Transplantation. ",

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Weber, S, Thiele, H, Mir, S, Toliat, MR, Sozeri, B, Reutter, H, Draaken, M, Ludwig, M, Altmüller, J, Frommolt, P, Stuart, HM, Ranjzad, P, Hanley, NA, Jennings, R, Newman, WG, Wilcox, DT, Thiel, U, Schlingmann, KP, Beetz, R, Hoyer, PF, Konrad, M, Schaefer, F, Nürnberg, P & Woolf, AS 2011, 'Muscarinic acetylcholine receptor m3 mutation causes urinary bladder disease and a prune-belly-like syndrome', American Journal of Human Genetics, vol. 89, no. 5, pp. 668-674. https://doi.org/10.1016/j.ajhg.2011.10.007

TY - JOUR

T1 - Muscarinic acetylcholine receptor m3 mutation causes urinary bladder disease and a prune-belly-like syndrome

AU - Weber, Stefanie

AU - Thiele, Holger

AU - Mir, Sevgi

AU - Toliat, Mohammad Reza

AU - Sozeri, Betül

AU - Reutter, Heiko

AU - Draaken, Markus

AU - Ludwig, Michael

AU - Altmüller, Janine

AU - Frommolt, Peter

AU - Stuart, Helen M.

AU - Ranjzad, Parisa

AU - Hanley, Neil A.

AU - Jennings, Rachel

AU - Newman, William G.

AU - Wilcox, Duncan T.

AU - Thiel, Uwe

AU - Schlingmann, Karl Peter

AU - Beetz, Rolf

AU - Hoyer, Peter F.

AU - Konrad, Martin

AU - Schaefer, Franz

AU - Nürnberg, Peter

AU - Woolf, Adrian S.

N1 - Funding Information: We thank the patients and their family for participating in this study, Bettina Cirkel and Christian Becker for excellent technical support and Anne Deix for critical advice. Financial grant support was received from the Kidney Research UK (W.G.N. and A.S.W.), Kids Kidney Research and Kidneys for Life (A.S.W.), Manchester NIHR Biomedical Research Centre (A.S.W., R.J., N.A.H., H.S., and W.G.N.), and The Wellcome Trust (A.S.W. and N.A.H.). S.W. and F.S. received financial support from the Fritz Thyssen grant. H.R. and M.D. are members of the German network for congenital uro-rectal malformations (CURE-Net), which is supported by a research grant (01GM08107) from the German Federal Ministry of Education and Research. The 4C-Kidney Disease Study is supported by research grants of the KfH Foundation for Preventive Medicine, ERA-EDTA and IFB Transplantation.

PY - 2011/11/11

Y1 - 2011/11/11

N2 - Urinary bladder malformations associated with bladder outlet obstruction are a frequent cause of progressive renal failure in children. We here describe a muscarinic acetylcholine receptor M3 (CHRM3) (1q41-q44) homozygous frameshift mutation in familial congenital bladder malformation associated with a prune-belly-like syndrome, defining an isolated gene defect underlying this sometimes devastating disease. CHRM3 encodes the M3 muscarinic acetylcholine receptor, which we show is present in developing renal epithelia and bladder muscle. These observations may imply that M3 has a role beyond its known contribution to detrusor contractions. This Mendelian disease caused by a muscarinic acetylcholine receptor mutation strikingly phenocopies Chrm3 null mutant mice.

AB - Urinary bladder malformations associated with bladder outlet obstruction are a frequent cause of progressive renal failure in children. We here describe a muscarinic acetylcholine receptor M3 (CHRM3) (1q41-q44) homozygous frameshift mutation in familial congenital bladder malformation associated with a prune-belly-like syndrome, defining an isolated gene defect underlying this sometimes devastating disease. CHRM3 encodes the M3 muscarinic acetylcholine receptor, which we show is present in developing renal epithelia and bladder muscle. These observations may imply that M3 has a role beyond its known contribution to detrusor contractions. This Mendelian disease caused by a muscarinic acetylcholine receptor mutation strikingly phenocopies Chrm3 null mutant mice.

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U2 - 10.1016/j.ajhg.2011.10.007

DO - 10.1016/j.ajhg.2011.10.007

M3 - Article

C2 - 22077972

AN - SCOPUS:80955135797

SN - 0002-9297

VL - 89

SP - 668

EP - 674

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 5

ER -

Muscarinic acetylcholine receptor m3 mutation causes urinary bladder disease and a prune-belly-like syndrome

Abstract

Bibliographical note

ASJC Scopus subject areas

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