Identification of mutations in CUL7 in 3-M syndrome

Céline Huber; Dora Dias-Santagata; Anna Glaser; James O'Sullivan; Raja Brauner; Kenneth Wu; Xinsong Xu; Kerra Pearce; Rong Wang; Maria Luisa Giovannucci Uzielli; Nathalie Dagoneau; Wassim Chemaitilly; Andrea Superti-Furga; Heloisa Dos Santos; André Mégarbané; Gilles Morin; Gabriele Gillessen-Kaesbach; Raoul Hennekam; Ineke Van Der Burgt; Graeme C.M. Black; Peter E. Clayton; Andrew Read; Martine Le Merrer; Peter J. Scambler; Arnold Munnich; Zhen Qiang Pan; Robin Winter; Valérie Cormier-Daire

doi:10.1038/ng1628

Identification of mutations in CUL7 in 3-M syndrome

Céline Huber, Dora Dias-Santagata, Anna Glaser, James O'Sullivan, Raja Brauner, Kenneth Wu, Xinsong Xu, Kerra Pearce, Rong Wang, Maria Luisa Giovannucci Uzielli, Nathalie Dagoneau, Wassim Chemaitilly, Andrea Superti-Furga, Heloisa Dos Santos, André Mégarbané, Gilles Morin, Gabriele Gillessen-Kaesbach, Raoul Hennekam, Ineke Van Der Burgt, Graeme C.M. BlackPeter E. Clayton, Andrew Read, Martine Le Merrer, Peter J. Scambler, Arnold Munnich, Zhen Qiang Pan, Robin Winter, Valérie Cormier-Daire^*

^*Corresponding author for this work

Institute of Human Genetics

125 Citations (Scopus)

Abstract

Intrauterine growth retardation is caused by maternal, fetal or placental factors that result in impaired endovascular trophoblast invasion and reduced placental perfusion. Although various causes of intrauterine growth retardation have been identified, most cases remain unexplained. Studying 29 families with 3-M syndrome (OMIM 273750), an autosomal recessive condition characterized by severe pre- and postnatal growth retardation, we first mapped the underlying gene to chromosome 6p21.1 and then identified 25 distinct mutations in the gene cullin 7 (CUL7). CUL7 assembles an E3 ubiquitin ligase complex containing Skp1, Fbx29 (also called Fbw8) and ROC1 and promotes ubiquitination. Using deletion analysis, we found that CUL7 uses its central region to interact with the Skp1-Fbx29 heterodimer. Functional studies indicated that the 3-M-associated CUL7 nonsense and missense mutations R1445X and H1464P, respectively, render CUL7 deficient in recruiting ROC1. These results suggest that impaired ubiquitination may have a role in the pathogenesis of intrauterine growth retardation in humans.

Original language	English
Journal	Nature Genetics
Volume	37
Issue number	10
Pages (from-to)	1119-1124
Number of pages	6
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng1628
Publication status	Published - 10.2005

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Research Area: Medical Genetics

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Huber, C., Dias-Santagata, D., Glaser, A., O'Sullivan, J., Brauner, R., Wu, K., Xu, X., Pearce, K., Wang, R., Uzielli, M. L. G., Dagoneau, N., Chemaitilly, W., Superti-Furga, A., Dos Santos, H., Mégarbané, A., Morin, G., Gillessen-Kaesbach, G., Hennekam, R., Van Der Burgt, I., ... Cormier-Daire, V. (2005). Identification of mutations in CUL7 in 3-M syndrome. Nature Genetics, 37(10), 1119-1124. https://doi.org/10.1038/ng1628

@article{f411345fd29d49f6adebdc2a02f3feb2,

title = "Identification of mutations in CUL7 in 3-M syndrome",

abstract = "Intrauterine growth retardation is caused by maternal, fetal or placental factors that result in impaired endovascular trophoblast invasion and reduced placental perfusion. Although various causes of intrauterine growth retardation have been identified, most cases remain unexplained. Studying 29 families with 3-M syndrome (OMIM 273750), an autosomal recessive condition characterized by severe pre- and postnatal growth retardation, we first mapped the underlying gene to chromosome 6p21.1 and then identified 25 distinct mutations in the gene cullin 7 (CUL7). CUL7 assembles an E3 ubiquitin ligase complex containing Skp1, Fbx29 (also called Fbw8) and ROC1 and promotes ubiquitination. Using deletion analysis, we found that CUL7 uses its central region to interact with the Skp1-Fbx29 heterodimer. Functional studies indicated that the 3-M-associated CUL7 nonsense and missense mutations R1445X and H1464P, respectively, render CUL7 deficient in recruiting ROC1. These results suggest that impaired ubiquitination may have a role in the pathogenesis of intrauterine growth retardation in humans.",

author = "C{\'e}line Huber and Dora Dias-Santagata and Anna Glaser and James O'Sullivan and Raja Brauner and Kenneth Wu and Xinsong Xu and Kerra Pearce and Rong Wang and Uzielli, {Maria Luisa Giovannucci} and Nathalie Dagoneau and Wassim Chemaitilly and Andrea Superti-Furga and {Dos Santos}, Heloisa and Andr{\'e} M{\'e}garban{\'e} and Gilles Morin and Gabriele Gillessen-Kaesbach and Raoul Hennekam and {Van Der Burgt}, Ineke and Black, {Graeme C.M.} and Clayton, {Peter E.} and Andrew Read and {Le Merrer}, Martine and Scambler, {Peter J.} and Arnold Munnich and Pan, {Zhen Qiang} and Robin Winter and Val{\'e}rie Cormier-Daire",

note = "Funding Information: comments. Part of this work was supported by European Skeletal Dysplasia Network. Z.-Q.P. and R.W. are supported by Public Health Service grants. K.P. was funded by the London IDEAS genetics knowledge park, and P.J.S. was supported by the BDF Newlife and British Heart Foundation. J.O. was funded by the BDF Newlife. G.C.M.B. is a Wellcome Trust Senior Clinical Research Fellow. This manuscript is dedicated to the memory of Robin Winter.",

year = "2005",

month = oct,

doi = "10.1038/ng1628",

language = "English",

volume = "37",

pages = "1119--1124",

journal = "Nature Genetics",

issn = "1061-4036",

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}

Huber, C, Dias-Santagata, D, Glaser, A, O'Sullivan, J, Brauner, R, Wu, K, Xu, X, Pearce, K, Wang, R, Uzielli, MLG, Dagoneau, N, Chemaitilly, W, Superti-Furga, A, Dos Santos, H, Mégarbané, A, Morin, G, Gillessen-Kaesbach, G, Hennekam, R, Van Der Burgt, I, Black, GCM, Clayton, PE, Read, A, Le Merrer, M, Scambler, PJ, Munnich, A, Pan, ZQ, Winter, R & Cormier-Daire, V 2005, 'Identification of mutations in CUL7 in 3-M syndrome', Nature Genetics, vol. 37, no. 10, pp. 1119-1124. https://doi.org/10.1038/ng1628

TY - JOUR

T1 - Identification of mutations in CUL7 in 3-M syndrome

AU - Huber, Céline

AU - Dias-Santagata, Dora

AU - Glaser, Anna

AU - O'Sullivan, James

AU - Brauner, Raja

AU - Wu, Kenneth

AU - Xu, Xinsong

AU - Pearce, Kerra

AU - Wang, Rong

AU - Uzielli, Maria Luisa Giovannucci

AU - Dagoneau, Nathalie

AU - Chemaitilly, Wassim

AU - Superti-Furga, Andrea

AU - Dos Santos, Heloisa

AU - Mégarbané, André

AU - Morin, Gilles

AU - Gillessen-Kaesbach, Gabriele

AU - Hennekam, Raoul

AU - Van Der Burgt, Ineke

AU - Black, Graeme C.M.

AU - Clayton, Peter E.

AU - Read, Andrew

AU - Le Merrer, Martine

AU - Scambler, Peter J.

AU - Munnich, Arnold

AU - Pan, Zhen Qiang

AU - Winter, Robin

AU - Cormier-Daire, Valérie

N1 - Funding Information: comments. Part of this work was supported by European Skeletal Dysplasia Network. Z.-Q.P. and R.W. are supported by Public Health Service grants. K.P. was funded by the London IDEAS genetics knowledge park, and P.J.S. was supported by the BDF Newlife and British Heart Foundation. J.O. was funded by the BDF Newlife. G.C.M.B. is a Wellcome Trust Senior Clinical Research Fellow. This manuscript is dedicated to the memory of Robin Winter.

PY - 2005/10

Y1 - 2005/10

N2 - Intrauterine growth retardation is caused by maternal, fetal or placental factors that result in impaired endovascular trophoblast invasion and reduced placental perfusion. Although various causes of intrauterine growth retardation have been identified, most cases remain unexplained. Studying 29 families with 3-M syndrome (OMIM 273750), an autosomal recessive condition characterized by severe pre- and postnatal growth retardation, we first mapped the underlying gene to chromosome 6p21.1 and then identified 25 distinct mutations in the gene cullin 7 (CUL7). CUL7 assembles an E3 ubiquitin ligase complex containing Skp1, Fbx29 (also called Fbw8) and ROC1 and promotes ubiquitination. Using deletion analysis, we found that CUL7 uses its central region to interact with the Skp1-Fbx29 heterodimer. Functional studies indicated that the 3-M-associated CUL7 nonsense and missense mutations R1445X and H1464P, respectively, render CUL7 deficient in recruiting ROC1. These results suggest that impaired ubiquitination may have a role in the pathogenesis of intrauterine growth retardation in humans.

AB - Intrauterine growth retardation is caused by maternal, fetal or placental factors that result in impaired endovascular trophoblast invasion and reduced placental perfusion. Although various causes of intrauterine growth retardation have been identified, most cases remain unexplained. Studying 29 families with 3-M syndrome (OMIM 273750), an autosomal recessive condition characterized by severe pre- and postnatal growth retardation, we first mapped the underlying gene to chromosome 6p21.1 and then identified 25 distinct mutations in the gene cullin 7 (CUL7). CUL7 assembles an E3 ubiquitin ligase complex containing Skp1, Fbx29 (also called Fbw8) and ROC1 and promotes ubiquitination. Using deletion analysis, we found that CUL7 uses its central region to interact with the Skp1-Fbx29 heterodimer. Functional studies indicated that the 3-M-associated CUL7 nonsense and missense mutations R1445X and H1464P, respectively, render CUL7 deficient in recruiting ROC1. These results suggest that impaired ubiquitination may have a role in the pathogenesis of intrauterine growth retardation in humans.

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U2 - 10.1038/ng1628

DO - 10.1038/ng1628

M3 - Journal articles

C2 - 16142236

AN - SCOPUS:27144498420

SN - 1061-4036

VL - 37

SP - 1119

EP - 1124

JO - Nature Genetics

JF - Nature Genetics

IS - 10

ER -

Identification of mutations in CUL7 in 3-M syndrome

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