Roessler, Erich and El-Jaick, Kenia B. and Dubourg, Christele and Velez, Jorge I. and Solomon, Benjamin D. and Pineda-Alvarez, Daniel E. and Lacbawan, Felicitas and Zhou, Nan and Ouspenskaia, Maia and Paulussen, Aimee and Smeets, Hubert J. and Hehr, Ute and Bendavid, Claude and Bale, Sherri and Odent, Sylvie and David, Veronique and Muenke, Maximilian (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. HUMAN MUTATION, 30 (10). E921-E935. ISSN 1059-7794, 1098-1004
Full text not available from this repository. (Request a copy)Abstract
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 (C) 2009 WileyLiss, Inc.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MAXILLARY CENTRAL INCISOR; SONIC-HEDGEHOG GENE; BRACHYDACTYLY TYPE A1; HUMAN SIX3 GENE; GONADAL-DYSGENESIS; DESERT-HEDGEHOG; INDIAN HEDGEHOG; HETEROZYGOUS MUTATION; CRYSTAL-STRUCTURE; TERMINAL DOMAIN; holoprosencephaly; mutation spectrum; SHH; protein processing |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 04 Sep 2020 05:06 |
| Last Modified: | 04 Sep 2020 05:06 |
| URI: | https://pred.uni-regensburg.de/id/eprint/28343 |
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