Research ExplorerPublicationsMutations in WNT1 cause different forms of bone fragility

Mutations in WNT1 cause different forms of bone fragility

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Mutations in WNT1 cause different forms of bone fragility. / Keupp, Katharina; Beleggia, Filippo; Kayserili, Hülya; Barnes, Aileen M; Steiner, Magdalena; Semler, Oliver; Fischer, Björn; Yigit, Gökhan; Janda, Claudia Y; Becker, Jutta; Breer, Stefan; Altunoglu, Umut; Grünhagen, Johannes; Krawitz, Peter; Hecht, Jochen; Schinke, Thorsten; Makareeva, Elena; Lausch, Ekkehart; Cankaya, Tufan; Caparrós-Martín, José A; Lapunzina, Pablo; Temtamy, Samia; Aglan, Mona; Zabel, Bernhard; Eysel, Peer; Koerber, Friederike; Leikin, Sergey; Garcia, K Christopher; Netzer, Christian; Schönau, Eckhard; Ruiz-Perez, Victor L; Mundlos, Stefan; Amling, Michael; Kornak, Uwe; Marini, Joan; Wollnik, Bernd.

In: AM J HUM GENET, Vol. 92, No. 4, 04.04.2013, p. 565-74.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Keupp, K, Beleggia, F, Kayserili, H, Barnes, AM, Steiner, M, Semler, O, Fischer, B, Yigit, G, Janda, CY, Becker, J, Breer, S, Altunoglu, U, Grünhagen, J, Krawitz, P, Hecht, J, Schinke, T, Makareeva, E, Lausch, E, Cankaya, T, Caparrós-Martín, JA, Lapunzina, P, Temtamy, S, Aglan, M, Zabel, B, Eysel, P, Koerber, F, Leikin, S, Garcia, KC, Netzer, C, Schönau, E, Ruiz-Perez, VL, Mundlos, S, Amling, M, Kornak, U, Marini, J & Wollnik, B 2013, 'Mutations in WNT1 cause different forms of bone fragility', AM J HUM GENET, vol. 92, no. 4, pp. 565-74. https://doi.org/10.1016/j.ajhg.2013.02.010

APA

Keupp, K., Beleggia, F., Kayserili, H., Barnes, A. M., Steiner, M., Semler, O., Fischer, B., Yigit, G., Janda, C. Y., Becker, J., Breer, S., Altunoglu, U., Grünhagen, J., Krawitz, P., Hecht, J., Schinke, T., Makareeva, E., Lausch, E., Cankaya, T., ... Wollnik, B. (2013). Mutations in WNT1 cause different forms of bone fragility. AM J HUM GENET, 92(4), 565-74. https://doi.org/10.1016/j.ajhg.2013.02.010

Vancouver

Keupp K, Beleggia F, Kayserili H, Barnes AM, Steiner M, Semler O et al. Mutations in WNT1 cause different forms of bone fragility. AM J HUM GENET. 2013 Apr 4;92(4):565-74. https://doi.org/10.1016/j.ajhg.2013.02.010

Bibtex

@article{d8dc143e565d4c1bac556120ad54f516,
title = "Mutations in WNT1 cause different forms of bone fragility",
abstract = "We report that hypofunctional alleles of WNT1 cause autosomal-recessive osteogenesis imperfecta, a congenital disorder characterized by reduced bone mass and recurrent fractures. In consanguineous families, we identified five homozygous mutations in WNT1: one frameshift mutation, two missense mutations, one splice-site mutation, and one nonsense mutation. In addition, in a family affected by dominantly inherited early-onset osteoporosis, a heterozygous WNT1 missense mutation was identified in affected individuals. Initial functional analysis revealed that altered WNT1 proteins fail to activate canonical LRP5-mediated WNT-regulated β-catenin signaling. Furthermore, osteoblasts cultured in vitro showed enhanced Wnt1 expression with advancing differentiation, indicating a role of WNT1 in osteoblast function and bone development. Our finding that homozygous and heterozygous variants in WNT1 predispose to low-bone-mass phenotypes might advance the development of more effective therapeutic strategies for congenital forms of bone fragility, as well as for common forms of age-related osteoporosis.",
keywords = "Animals, Base Sequence, Bone Density, Bone and Bones, Cells, Cultured, Child, Child, Preschool, Female, Heterozygote, Humans, Infant, Newborn, LDL-Receptor Related Proteins, Male, Mice, Mice, Inbred C57BL, Molecular Sequence Data, Mutation, Osteoblasts, Osteogenesis Imperfecta, Osteoporosis, Pedigree, Phenotype, Pregnancy, Wnt1 Protein",
author = "Katharina Keupp and Filippo Beleggia and H{\"u}lya Kayserili and Barnes, {Aileen M} and Magdalena Steiner and Oliver Semler and Bj{\"o}rn Fischer and G{\"o}khan Yigit and Janda, {Claudia Y} and Jutta Becker and Stefan Breer and Umut Altunoglu and Johannes Gr{\"u}nhagen and Peter Krawitz and Jochen Hecht and Thorsten Schinke and Elena Makareeva and Ekkehart Lausch and Tufan Cankaya and Caparr{\'o}s-Mart{\'i}n, {Jos{\'e} A} and Pablo Lapunzina and Samia Temtamy and Mona Aglan and Bernhard Zabel and Peer Eysel and Friederike Koerber and Sergey Leikin and Garcia, {K Christopher} and Christian Netzer and Eckhard Sch{\"o}nau and Ruiz-Perez, {Victor L} and Stefan Mundlos and Michael Amling and Uwe Kornak and Joan Marini and Bernd Wollnik",
note = "Copyright {\textcopyright} 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.",
year = "2013",
month = apr,
day = "4",
doi = "10.1016/j.ajhg.2013.02.010",
language = "English",
volume = "92",
pages = "565--74",
journal = "AM J HUM GENET",
issn = "0002-9297",
publisher = "Cell Press",
number = "4",

}

RIS

TY - JOUR

T1 - Mutations in WNT1 cause different forms of bone fragility

AU - Keupp, Katharina

AU - Beleggia, Filippo

AU - Kayserili, Hülya

AU - Barnes, Aileen M

AU - Steiner, Magdalena

AU - Semler, Oliver

AU - Fischer, Björn

AU - Yigit, Gökhan

AU - Janda, Claudia Y

AU - Becker, Jutta

AU - Breer, Stefan

AU - Altunoglu, Umut

AU - Grünhagen, Johannes

AU - Krawitz, Peter

AU - Hecht, Jochen

AU - Schinke, Thorsten

AU - Makareeva, Elena

AU - Lausch, Ekkehart

AU - Cankaya, Tufan

AU - Caparrós-Martín, José A

AU - Lapunzina, Pablo

AU - Temtamy, Samia

AU - Aglan, Mona

AU - Zabel, Bernhard

AU - Eysel, Peer

AU - Koerber, Friederike

AU - Leikin, Sergey

AU - Garcia, K Christopher

AU - Netzer, Christian

AU - Schönau, Eckhard

AU - Ruiz-Perez, Victor L

AU - Mundlos, Stefan

AU - Amling, Michael

AU - Kornak, Uwe

AU - Marini, Joan

AU - Wollnik, Bernd

N1 - Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

PY - 2013/4/4

Y1 - 2013/4/4

N2 - We report that hypofunctional alleles of WNT1 cause autosomal-recessive osteogenesis imperfecta, a congenital disorder characterized by reduced bone mass and recurrent fractures. In consanguineous families, we identified five homozygous mutations in WNT1: one frameshift mutation, two missense mutations, one splice-site mutation, and one nonsense mutation. In addition, in a family affected by dominantly inherited early-onset osteoporosis, a heterozygous WNT1 missense mutation was identified in affected individuals. Initial functional analysis revealed that altered WNT1 proteins fail to activate canonical LRP5-mediated WNT-regulated β-catenin signaling. Furthermore, osteoblasts cultured in vitro showed enhanced Wnt1 expression with advancing differentiation, indicating a role of WNT1 in osteoblast function and bone development. Our finding that homozygous and heterozygous variants in WNT1 predispose to low-bone-mass phenotypes might advance the development of more effective therapeutic strategies for congenital forms of bone fragility, as well as for common forms of age-related osteoporosis.

AB - We report that hypofunctional alleles of WNT1 cause autosomal-recessive osteogenesis imperfecta, a congenital disorder characterized by reduced bone mass and recurrent fractures. In consanguineous families, we identified five homozygous mutations in WNT1: one frameshift mutation, two missense mutations, one splice-site mutation, and one nonsense mutation. In addition, in a family affected by dominantly inherited early-onset osteoporosis, a heterozygous WNT1 missense mutation was identified in affected individuals. Initial functional analysis revealed that altered WNT1 proteins fail to activate canonical LRP5-mediated WNT-regulated β-catenin signaling. Furthermore, osteoblasts cultured in vitro showed enhanced Wnt1 expression with advancing differentiation, indicating a role of WNT1 in osteoblast function and bone development. Our finding that homozygous and heterozygous variants in WNT1 predispose to low-bone-mass phenotypes might advance the development of more effective therapeutic strategies for congenital forms of bone fragility, as well as for common forms of age-related osteoporosis.

KW - Animals

KW - Base Sequence

KW - Bone Density

KW - Bone and Bones

KW - Cells, Cultured

KW - Child

KW - Child, Preschool

KW - Female

KW - Heterozygote

KW - Humans

KW - Infant, Newborn

KW - LDL-Receptor Related Proteins

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Molecular Sequence Data

KW - Mutation

KW - Osteoblasts

KW - Osteogenesis Imperfecta

KW - Osteoporosis

KW - Pedigree

KW - Phenotype

KW - Pregnancy

KW - Wnt1 Protein

U2 - 10.1016/j.ajhg.2013.02.010

DO - 10.1016/j.ajhg.2013.02.010

M3 - SCORING: Journal article

C2 - 23499309

VL - 92

SP - 565

EP - 574

JO - AM J HUM GENET

JF - AM J HUM GENET

SN - 0002-9297

IS - 4

ER -