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Holoprosencephaly: new models, new insights

Published online by Cambridge University Press:  24 September 2007

Robert S. Krauss
Robert S. Krauss
Affiliation:
Department of Molecular, Cell and Developmental Biology, Mount Sinai School of Medicine, New York, NY 10029, USA. Tel: +1 212 241 2177; Fax: +2 212 860 9279; E-mail: Robert.Krauss@mssm.edu
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Abstract

Holoprosencephaly (HPE) is a common congenital malformation that is characterised by a failure to divide the forebrain into left and right hemispheres and is usually accompanied by defects in patterning of the midline of the face. HPE exists in inherited, autosomal dominant (familial) forms and mutation-associated sporadic forms, but environmental factors are also implicated. There are several features of HPE that are not well understood, including the extremely variable clinical presentation, even among obligate carriers of familial mutations, and the restriction of structural anomalies to the ventral anterior midline, despite association with defects in signal transduction pathways that regulate development of many additional body structures. The new animal models described in this review may help unravel these puzzles. Furthermore, these model systems suggest that human HPE arises from a complex interaction between the timing and strength of developmental signalling pathways, genetic variation and exposure to environmental agents.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 9 , Issue 26 , September 2007 , pp. 1 - 17
Copyright
Copyright © Cambridge University Press 2007

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References

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Further reading, resources and contacts

Muenke, M. and Beachy, P.A. (2001) Holoprosencephaly. In The Metabolic & Molecular Bases of Inherited Disease (Scriver, C. R. et al. ed.), pp. 6203–6230. McGraw-Hill, New YorkGoogle Scholar
Yamada, S. et al. (2004) Phenotypic variability in human embryonic holoprosencephaly in the Kyoto Collection. Birth Defects Res Part A Clin Mol Teratol 70, 495–508Google Scholar
Cohen, M.M. Jr. (2006) Holoprosencephaly: clinical, anatomic, and molecular dimensions. Birth Defects Res Part A Clin Mol Teratol 76, 658–673Google Scholar
Dubourg, C. et al. (2007) Holoprosencephaly. Orphanet J Rare Dis 2, 8CrossRefGoogle ScholarPubMed
Ming, J.E. and Muenke, M. (2002) Multiple hits during early embryonic development: digenic diseases and holoprosencephaly. Am J Hum Genet 71, 1017–1032Google Scholar
http://www.ninds.nih.gov/disorders/holoprosencephaly/holoprosencephaly.htmGoogle Scholar
http://www.stanford.edu/group/hpe/Google Scholar