Journal Article

Expression of the <i>Sonic hedgehog (SHH)</i> Gene during Early Human Development and Phenotypic Expression of New Mutations Causing Holoprosencephaly

S. Odent, T. Attié-Bitach, M. Blayau, M. Mathieu, J. Augé, A.L. Delezoïde, J.Y. Le Gall, B. Le Marec, A. Munnich, V. David and M. Vekemans

in Human Molecular Genetics

Volume 8, issue 9, pages 1683-1689
Published in print September 1999 | ISSN: 0964-6906
Published online September 1999 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/8.9.1683
Expression of the Sonic hedgehog (SHH) Gene during Early Human Development and Phenotypic Expression of New Mutations Causing Holoprosencephaly

Show Summary Details

Preview

Holoprosencephaly (HPE), the most common developmental defect of the forebrain and the face, is genetically heterogeneous. One of the genes involved, Sonic hedgehog (SHH), on 7q36, has been identified as the first HPE-causing gene both in mouse and humans. In order to delineate the phenotype of specific SHH mutations, we described the expression of the SHH gene during early human embryogenesis and investigated the phenotype of novel SHH mutations. In situ hybridization studies were performed on paraffin-embedded human embryo sections at three different development stages. These studies show that SHH is expressed in the notochord, the floorplate, the brain, the zone of polarizing activity and the gut. We also report on the phenotype of four novel mutations identified in 40 HPE families (two in isolated HPE and two in familial HPE). Expressivity ranged from alobar HPE to microcephaly and hypoplasia of the pituitary gland in one family, and from HPE to an asymptomatic form in another family. No SHH mutation was found in six polymalformed cases combining HPE with other defects, such as skeletal, limb, cardiac, anal and/or renal anomalies. This study confirms the genetic heterogeneity of HPE, and further demonstrates that SHH mutations are associated with a broad spectrum of cerebral midline defects.

Journal Article.  4087 words.  Illustrated.

Subjects: Genetics and Genomics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.