Research Article

Clinical and molecular delineation of the Greig cephalopolysyndactyly contiguous gene deletion syndrome and its distinction from acrocallosal syndrome†‡

  1. Jennifer J. Johnston1,
  2. Isabelle Olivos-Glander1,2,
  3. Joyce Turner1,
  4. Kyrieckos Aleck3,
  5. Lynne M. Bird4,
  6. Lakshmi Mehta5,
  7. R. Neil Schimke6,
  8. Heidi Heilstedt7,
  9. J. Edward Spence8,
  10. Jan Blancato9,
  11. Leslie G. Biesecker1,*

Article first published online: 29 SEP 2003

DOI: 10.1002/ajmg.a.20318

Issue

American Journal of Medical Genetics Part A

American Journal of Medical Genetics Part A

Volume 123A, Issue 3, pages 236–242, 15 December 2003

Additional Information

How to Cite

Johnston, J. J., Olivos-Glander, I., Turner, J., Aleck, K., Bird, L. M., Mehta, L., Schimke, R. N., Heilstedt, H., Spence, J. E., Blancato, J. and Biesecker, L. G. (2003), Clinical and molecular delineation of the Greig cephalopolysyndactyly contiguous gene deletion syndrome and its distinction from acrocallosal syndrome. American Journal of Medical Genetics Part A, 123A: 236–242. doi: 10.1002/ajmg.a.20318

Author Information

  1. 1

    National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland

  2. 2

    GeneDx Corp., Gaithersburg, Maryland

  3. 3

    University of Arizona College of Medicine, Phoenix, Arizona

  4. 4

    Children's Hospital and Health Center, San Diego, California

  5. 5

    North Shore University Hospital, Manhasset, New York

  6. 6

    Kansas University Medical School, Kansas City, Kansas

  7. 7

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas

  8. 8

    Carolinas Medical Center, Charlotte, North Carolina

  9. 9

    Georgetown University Medical Center, Washington, DC

*NHGRI/NIH, Bldg 49, Room 4A80, Bethesda, MD 20892.

  1. †

    Jennifer J. Johnston and Isabelle Olivos-Glander contributed equally to this work.

  2. ‡

    This article was prepared by a group consisting of both United States Government employees and non-United States Government employees, and as such is subject to 117 U.S.C. Sec. 105.

Publication History

  1. Issue published online: 3 NOV 2003
  2. Article first published online: 29 SEP 2003
  3. Manuscript Accepted: 16 MAR 2003
  4. Manuscript Received: 19 NOV 2002

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Keywords:

  • GLI3;
  • GCPS;
  • acrocallosal

Abstract

Greig cephalopolysyndactyly syndrome (GCPS) is caused by haploinsufficiency of GLI3 on 7p13. Features of GCPS include polydactyly, macrocephaly, and hypertelorism, and may be associated with cognitive deficits and abnormalities of the corpus callosum. GLI3 mutations in GCPS patients include point, frameshift, translocation, and gross deletion mutations. FISH and STRP analyses were applied to 34 patients with characteristics of GCPS. Deletions were identified in 11 patients and the extent of their deletion was determined. Nine patients with deletions had mental retardation (MR) or developmental delay (DD) and were classified as severe GCPS. These severe GCPS patients have manifestations that overlap with the acrocallosal syndrome (ACLS). The deletion breakpoints were analyzed in six patients whose deletions ranged in size from 151 kb to 10.6 Mb. Junction fragments were found to be distinct with no common sequences flanking the breakpoints. We conclude that patients with GCPS caused by large deletions that include GLI3 are likely to have cognitive deficits, and we hypothesize that this severe GCPS phenotype is caused by deletion of contiguous genes. © 2003 Wiley-Liss, Inc.

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