Human Genetics

, Volume 100, Issue 2, pp 172–181

Cytogenetic rearrangements involving the loss of the Sonic Hedgehog gene at 7q36 cause holoprosencephaly

  • Erich Roessler
  • Deeann E. Ward
  • Karin Gaudenz
  • Elena Belloni
  • Steven W. Scherer
  • Dian Donnai
  • Jacqueline Siegel-Bartelt
  • Lap-Chee Tsui
  • M. Muenke
Original investigation

DOI: 10.1007/s004390050486

Cite this article as:
Roessler, E., Ward, D., Gaudenz, K. et al. Hum Genet (1997) 100: 172. doi:10.1007/s004390050486

Abstract

Holoprosencephaly (HPE) is a genetically heterogeneous disorder that affects the midline development of the forebrain and midface in humans. As a step toward identifying one of the HPE genes, we have set out to refine the HPE3 critical region on human chromosome 7q36 by analyzing 34 cell lines from families with cytogenetic abnormalities involving 7q, 24 of which are associated with HPE. Genomic clones surrounding the DNA marker D7S104, which has previously been shown to be in the HPE3 critical region, have been examined by fluorescent in situ hybridization and microsatellite analysis of our panel of patient cell lines. We report the analysis of a cluster of four translocation breakpoints within a 300-kb region of 7q36 that serves to define the minimal critical region for HPE3 and that has directed the search for candidate genes. The human Sonic Hedgehog (hSHH) gene maps to this region and has been shown to be HPE3 on the basis of mutations within the coding region of the gene. We present evidence that cytogenetic deletions and/or rearrangements of this region of chromosome 7q containing Sonic Hedgehog, and translocations that may suppress Sonic Hedgehog gene expression through a position effect are common mechanisms leading to HPE.

Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • Erich Roessler
    • 1
  • Deeann E. Ward
    • 1
  • Karin Gaudenz
    • 1
  • Elena Belloni
    • 2
  • Steven W. Scherer
    • 2
  • Dian Donnai
    • 3
  • Jacqueline Siegel-Bartelt
    • 2
  • Lap-Chee Tsui
    • 2
  • M. Muenke
    • 1
  1. 1.The Children’s Hospital of Philadelphia, Division of Human Genetics and Molecular Biology, Department of Pediatrics and Genetics, University of Pennsylvania School of Medicine, 34th and Civic Center Boulevard, Philadelphia, PA 19104-4399, USA Tel.: +1-215-590-3859; Fax: +1-215-590-3850; e-mail: muenke@mail.med.upenn.eduUS
  2. 2.Department of Genetics, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G1X8, CanadaCA
  3. 3.Department of Clinical Genetics, St. Mary’s Hospital, Manchester, UKGB

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