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A recurrent mutation in MED12 leading to R961W causes Opitz-Kaveggia syndrome

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.

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Figure 1: Identification of a recurrent MED12 mutation in six families with Opitz-Kaveggia syndrome.

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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).

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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.

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Correspondence to Michael J Friez.

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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)

Supplementary Note (PDF 55 kb)

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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

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