Abstract
Opitz-Kaveggia syndrome (also known as FG syndrome) is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation. We report here that the original family for whom the condition is named and five other families have a recurrent mutation (2881C>T, leading to R961W) in MED12 (also called TRAP230 or HOPA), a gene located at Xq13 that functions as a thyroid receptor–associated protein in the Mediator complex.
Similar content being viewed by others
References
Kleefstra, T. et al. Clin. Genet. 67, 451–467 (2005).
Opitz, J.M. et al. Z. Kinderheilkd. 117, 1–18 (1974).
Philibert, R.A. et al. Mol. Psychiatry 3, 303–309 (1998).
Friez, M.J. et al. Hum. Genet. 106, 36–39 (2000).
Beyer, K.S. et al. Am. J. Med. Genet. 114, 110–115 (2002).
Schwartz, C.E. et al. Am. J. Hum. Genet. 77, 41–53 (2005).
Janody, F. et al. Development 130, 3691–3701 (2003).
Hong, S.K. et al. Proc. Natl. Acad. Sci. USA 102, 18473–18478 (2005).
Rau, M.J. et al. Dev. Biol. 296, 83–93 (2006).
Wang, X. et al. Proc. Natl. Acad. Sci. USA 103, 17284–17289 (2006).
Zhou, H. et al. Mol. Cell. Biol. 26, 8667–8682 (2006).
Kim, S. et al. J. Biol. Chem. 281, 14066–14075 (2006).
Lehner, B. et al. Nat. Genet. 38, 896–903 (2006).
Briault, S. et al. Am. J. Med. Genet. 73, 87–90 (1997).
Battaglia, A. et al. Am. J. Med. Genet. A. 140, 2075–2079 (2006).
Acknowledgements
Foremost, we thank the members of all the families for their cooperation and willingness to participate in this research. We also thank E. Smith, J. Nilsson, B. Bearden and J. John at the Greenwood Genetic Center for their technical contributions. This work was supported, in part, by grant HD 26202 from the US National Institute of Child Health and Human Development (to C.E.S.) as well as support from the South Carolina Department of Disabilities and Special Needs. J.M.G. acknowledges support from SHARE's Childhood Disability Center, the Steven Spielberg Pediatric Research Center and the Cedars-Sinai Burns and Allen Research Institute. This article is dedicated to the memory of E.F. Schwartz (1996–1998).
Author information
Authors and Affiliations
Contributions
H.R., S.J. and M.M. performed the sequencing analysis and segregation studies. J.G., R.C., R.C.R., J.O. and J.M. provided the patient material and clinical information. A.P. served as sample coordinator. J.J., C.S., R.S. and M.F. all contributed to the design of the study and writing of this paper.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
Supplementary Fig. 1
Sequencing electropherogram. (PDF 142 kb)
Supplementary Fig. 2
Protein sequence alignment. (PDF 17 kb)
Rights and permissions
About this article
Cite this article
Risheg, H., Graham, J., Clark, R. et al. A recurrent mutation in MED12 leading to R961W causes Opitz-Kaveggia syndrome. Nat Genet 39, 451–453 (2007). https://doi.org/10.1038/ng1992
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ng1992
- Springer Nature America, Inc.
This article is cited by
-
Auricular reconstruction: where are we now? A critical literature review
European Archives of Oto-Rhino-Laryngology (2022)
-
Novel MED12 variant in a multiplex Fragile X syndrome family: dual molecular etiology of two X-linked intellectual disabilities with autism in the same family
Molecular Biology Reports (2019)
-
Transcription regulation by the Mediator complex
Nature Reviews Molecular Cell Biology (2018)
-
MED31 involved in regulating self-renewal and adipogenesis of human mesenchymal stem cells
Molecular Biology Reports (2018)
-
Three-dimensional genome architecture and emerging technologies: looping in disease
Genome Medicine (2017)