Copy-number variations involving the IHH locus are associated with syndactyly and craniosynostosis

Eva Klopocki; Silke Lohan; Francesco Brancati; Randi Koll; Anja Brehm; Petra Seemann; Katarina Dathe; Sigmar Stricker; Jochen Hecht; Kristin Bosse; Regina C. Betz; Francesco Giuseppe Garaci; Bruno Dallapiccola; Mahim Jain; Maximilian Muenke; Vivian C.W. Ng; Wilson Chan; Danny Chan; Stefan Mundlos

doi:10.1016/j.ajhg.2010.11.006

Copy-number variations involving the IHH locus are associated with syndactyly and craniosynostosis

Eva Klopocki
, Silke Lohan
, Francesco Brancati
, Randi Koll
, Anja Brehm
, Petra Seemann
, Katarina Dathe
, Sigmar Stricker
, Jochen Hecht
, Kristin Bosse
, Regina C. Betz
, Francesco Giuseppe Garaci
, Bruno Dallapiccola
, Mahim Jain
, Maximilian Muenke
, Vivian C.W. Ng
, Wilson Chan
, Danny Chan
, Stefan Mundlos

Charité – Universitätsmedizin Berlin
Max Planck Institute for Molecular Genetics
Free University of Berlin
IRCCS Ospedale Casa Sollievo della Sofferenza - San Giovanni Rotondo (FG)
University of Rome Tor Vergata
Gabriele d'Annunzio University
Berlin-Brandenburg Center for Regenerative Therapies (BCRT)
University of Cologne
University of Bonn
IRCCS Ospedale pediatrico Bambino Gesù - Roma
Medical Genetics Branch
National Institutes of Health
The University of Hong Kong

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

84 Scopus citations

Abstract

Indian hedgehog (IHH) is a secreted signaling molecule of the hedgehog family known to play important roles in the regulation of chondrocyte differentiation, cortical bone formation, and the development of joints. Here, we describe that copy-number variations of the IHH locus involving conserved noncoding elements (CNEs) are associated with syndactyly and craniosynostosis. These CNEs are able to drive reporter gene expression in a pattern highly similar to wild-type Ihh expression. We postulate that the observed duplications lead to a misexpression and/or overexpression of IHH and by this affect the complex regulatory signaling network during digit and skull development.

Original language	English
Pages (from-to)	70-75
Number of pages	6
Journal	American Journal of Human Genetics
Volume	88
Issue number	1
DOIs	https://doi.org/10.1016/j.ajhg.2010.11.006
State	Published - 7 Jan 2011
Externally published	Yes

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Klopocki, E., Lohan, S., Brancati, F., Koll, R., Brehm, A., Seemann, P., Dathe, K., Stricker, S., Hecht, J., Bosse, K., Betz, R. C., Garaci, F. G., Dallapiccola, B., Jain, M., Muenke, M., Ng, V. C. W., Chan, W., Chan, D., & Mundlos, S. (2011). Copy-number variations involving the IHH locus are associated with syndactyly and craniosynostosis. American Journal of Human Genetics, 88(1), 70-75. https://doi.org/10.1016/j.ajhg.2010.11.006

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title = "Copy-number variations involving the IHH locus are associated with syndactyly and craniosynostosis",

abstract = "Indian hedgehog (IHH) is a secreted signaling molecule of the hedgehog family known to play important roles in the regulation of chondrocyte differentiation, cortical bone formation, and the development of joints. Here, we describe that copy-number variations of the IHH locus involving conserved noncoding elements (CNEs) are associated with syndactyly and craniosynostosis. These CNEs are able to drive reporter gene expression in a pattern highly similar to wild-type Ihh expression. We postulate that the observed duplications lead to a misexpression and/or overexpression of IHH and by this affect the complex regulatory signaling network during digit and skull development.",

author = "Eva Klopocki and Silke Lohan and Francesco Brancati and Randi Koll and Anja Brehm and Petra Seemann and Katarina Dathe and Sigmar Stricker and Jochen Hecht and Kristin Bosse and Betz, \{Regina C.\} and Garaci, \{Francesco Giuseppe\} and Bruno Dallapiccola and Mahim Jain and Maximilian Muenke and Ng, \{Vivian C.W.\} and Wilson Chan and Danny Chan and Stefan Mundlos",

year = "2011",

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doi = "10.1016/j.ajhg.2010.11.006",

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Klopocki, E, Lohan, S, Brancati, F, Koll, R, Brehm, A, Seemann, P, Dathe, K, Stricker, S, Hecht, J, Bosse, K, Betz, RC, Garaci, FG, Dallapiccola, B, Jain, M, Muenke, M, Ng, VCW, Chan, W, Chan, D & Mundlos, S 2011, 'Copy-number variations involving the IHH locus are associated with syndactyly and craniosynostosis', American Journal of Human Genetics, vol. 88, no. 1, pp. 70-75. https://doi.org/10.1016/j.ajhg.2010.11.006

TY - JOUR

T1 - Copy-number variations involving the IHH locus are associated with syndactyly and craniosynostosis

AU - Klopocki, Eva

AU - Lohan, Silke

AU - Brancati, Francesco

AU - Koll, Randi

AU - Brehm, Anja

AU - Seemann, Petra

AU - Dathe, Katarina

AU - Stricker, Sigmar

AU - Hecht, Jochen

AU - Bosse, Kristin

AU - Betz, Regina C.

AU - Garaci, Francesco Giuseppe

AU - Dallapiccola, Bruno

AU - Jain, Mahim

AU - Muenke, Maximilian

AU - Ng, Vivian C.W.

AU - Chan, Wilson

AU - Chan, Danny

AU - Mundlos, Stefan

PY - 2011/1/7

Y1 - 2011/1/7

N2 - Indian hedgehog (IHH) is a secreted signaling molecule of the hedgehog family known to play important roles in the regulation of chondrocyte differentiation, cortical bone formation, and the development of joints. Here, we describe that copy-number variations of the IHH locus involving conserved noncoding elements (CNEs) are associated with syndactyly and craniosynostosis. These CNEs are able to drive reporter gene expression in a pattern highly similar to wild-type Ihh expression. We postulate that the observed duplications lead to a misexpression and/or overexpression of IHH and by this affect the complex regulatory signaling network during digit and skull development.

AB - Indian hedgehog (IHH) is a secreted signaling molecule of the hedgehog family known to play important roles in the regulation of chondrocyte differentiation, cortical bone formation, and the development of joints. Here, we describe that copy-number variations of the IHH locus involving conserved noncoding elements (CNEs) are associated with syndactyly and craniosynostosis. These CNEs are able to drive reporter gene expression in a pattern highly similar to wild-type Ihh expression. We postulate that the observed duplications lead to a misexpression and/or overexpression of IHH and by this affect the complex regulatory signaling network during digit and skull development.

UR - https://www.scopus.com/pages/publications/78650911222

U2 - 10.1016/j.ajhg.2010.11.006

DO - 10.1016/j.ajhg.2010.11.006

M3 - Article

C2 - 21167467

AN - SCOPUS:78650911222

SN - 0002-9297

VL - 88

SP - 70

EP - 75

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 1

ER -

Copy-number variations involving the IHH locus are associated with syndactyly and craniosynostosis

Abstract

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