In the authors' opinion these individuals contributed equally to this work.
Mutation in Brief
Article first published online: 14 JUL 2009
This article is a US Government work and, as such, is in the public domain in the United States of America. Published in 2009 by Wiley-Liss, Inc.
Volume 30, Issue 10, pages E921–E935, October 2009
How to Cite
Roessler, E., El-Jaick, K. B., Dubourg, C., Vélez, J. I., Solomon, B. D., Pineda-Álvarez, D. E., Lacbawan, F., Zhou, N., Ouspenskaia, M., Paulussen, A., Smeets, H. J., Hehr, U., Bendavid, C., Bale, S., Odent, S., David, V. and Muenke, M. (2009), The mutational spectrum of holoprosencephaly-associated changes within the SHH gene in humans predicts loss-of-function through either key structural alterations of the ligand or its altered synthesis. Hum. Mutat., 30: E921–E935. doi: 10.1002/humu.21090
This article is a US Government work and, as such, is in the public domain in the United States of America.
Communicated by Ravi Savarirayan
- Issue published online: 28 SEP 2009
- Article first published online: 14 JUL 2009
- Manuscript Accepted: 26 JUN 2009
- Manuscript Received: 6 MAY 2009
- Cited By
- mutation spectrum;
- protein processing
Mutations within either the SHH gene or its related pathway components are the most common, and best understood, pathogenetic changes observed in holoprosencephaly patients; this fact is consistent with the essential functions of this gene during forebrain development and patterning. Here we summarize the nature and types of deleterious sequence alterations among over one hundred distinct mutations in the SHH gene (64 novel mutations) and compare these to over a dozen mutations in disease-related Hedgehog family members IHH and DHH. This combined structural analysis suggests that dysfunction of Hedgehog signaling in human forebrain development can occur through truncations or major structural changes to the signaling domain, SHH-N, as well as due to defects in the processing of the mature ligand from its pre-pro-precursor or defective post-translation bi-lipid modifications with palmitate and cholesterol Published 2009 by Wiley-Liss, Inc.