Brief Communication | Published:

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

Nature Genetics volume 39, pages 451453 (2007) | Download Citation



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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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


  1. Greenwood Genetic Center, Greenwood, South Carolina 29646, USA.

    • Hiba Risheg
    • , R Curtis Rogers
    • , Melanie May
    • , Sumy M Joseph
    • , Julie R Jones
    • , Roger E Stevenson
    • , Charles E Schwartz
    •  & Michael J Friez
  2. Medical Genetics Institute, Cedars-Sinai Medical Center, David Geffen School of Medicine at the University of California at Los Angeles (UCLA), Los Angeles, California 90048, USA.

    • John M Graham Jr
  3. Department of Pediatrics, Loma Linda University Children's Hospital, Loma Linda, California 92354, USA.

    • Robin D Clark
  4. Department of Pediatrics (Medical Genetics), Human Genetics, Pathology, Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.

    • John M Opitz
    •  & Andreas P Peiffer
  5. Clinical Genetics, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756, USA.

    • John B Moeschler


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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.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Michael J Friez.

Supplementary information

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  1. 1.

    Supplementary Fig. 1

    Sequencing electropherogram.

  2. 2.

    Supplementary Fig. 2

    Protein sequence alignment.

  3. 3.

    Supplementary Note

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