| pubmed-article:15292211 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:15292211 | lifeskim:mentions | umls-concept:C0079541 | lld:lifeskim |
| pubmed-article:15292211 | lifeskim:mentions | umls-concept:C0026882 | lld:lifeskim |
| pubmed-article:15292211 | lifeskim:mentions | umls-concept:C0205245 | lld:lifeskim |
| pubmed-article:15292211 | lifeskim:mentions | umls-concept:C0332281 | lld:lifeskim |
| pubmed-article:15292211 | lifeskim:mentions | umls-concept:C1335824 | lld:lifeskim |
| pubmed-article:15292211 | lifeskim:mentions | umls-concept:C1880022 | lld:lifeskim |
| pubmed-article:15292211 | pubmed:issue | 41 | lld:pubmed |
| pubmed-article:15292211 | pubmed:dateCreated | 2004-10-6 | lld:pubmed |
| pubmed-article:15292211 | pubmed:abstractText | Mutations of the developmental gene Sonic hedgehog (SHH) and alterations of SHH signaling have been associated with holoprosencephaly (HPE), a rare disorder characterized by a large spectrum of brain and craniofacial anomalies. Based on the crystal structure of mouse N-terminal and Drosophila C-terminal hedgehog proteins, we have developed three-dimensional models of the corresponding human proteins (SHH-N, SHH-C) that have allowed us to identify within these two domains crucial regions associated with HPE missense mutations. We have further characterized the functional consequences linked to 11 of these mutations. In transfected HEK293 cells, the production of the active SHH-N fragment was dramatically impaired for eight mutants (W117R, W117G, H140P, T150R, C183F, L271P, I354T, A383T). The supernatants from these cell cultures showed no significant SHH-signaling activity in a reporter cell-based assay. Two mutants (G31R, D222N) were associated with a lower production of SHH-N and signaling activity. Finally, one mutant harboring the A226T mutation displays an activity comparable with the wild-type protein. This work demonstrates that most of the HPE-associated SHH mutations analyzed have a deleterious effect on the availability of SHH-N and its biological activity. However, because of the lack of correlation between genotype and phenotype for SHH-associated mutations, our study suggests that other factors intervene in the development of the spectrum of HPE anomalies. | lld:pubmed |
| pubmed-article:15292211 | pubmed:language | eng | lld:pubmed |
| pubmed-article:15292211 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15292211 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:15292211 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:15292211 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15292211 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:15292211 | pubmed:month | Oct | lld:pubmed |
| pubmed-article:15292211 | pubmed:issn | 0021-9258 | lld:pubmed |
| pubmed-article:15292211 | pubmed:author | pubmed-author:FaureHélèneH | lld:pubmed |
| pubmed-article:15292211 | pubmed:author | pubmed-author:RuatMartialM | lld:pubmed |
| pubmed-article:15292211 | pubmed:author | pubmed-author:TraiffortElis... | lld:pubmed |
| pubmed-article:15292211 | pubmed:author | pubmed-author:DavidVéroniqu... | lld:pubmed |
| pubmed-article:15292211 | pubmed:author | pubmed-author:DubourgChrist... | lld:pubmed |
| pubmed-article:15292211 | pubmed:author | pubmed-author:RognanDidierD | lld:pubmed |
| pubmed-article:15292211 | pubmed:author | pubmed-author:OdentSylvieS | lld:pubmed |
| pubmed-article:15292211 | pubmed:author | pubmed-author:DurouMarie-Re... | lld:pubmed |
| pubmed-article:15292211 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:15292211 | pubmed:day | 8 | lld:pubmed |
| pubmed-article:15292211 | pubmed:volume | 279 | lld:pubmed |
| pubmed-article:15292211 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:15292211 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:15292211 | pubmed:pagination | 42889-97 | lld:pubmed |
| pubmed-article:15292211 | pubmed:dateRevised | 2006-11-15 | lld:pubmed |
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| pubmed-article:15292211 | pubmed:year | 2004 | lld:pubmed |
| pubmed-article:15292211 | pubmed:articleTitle | Functional characterization of sonic hedgehog mutations associated with holoprosencephaly. | lld:pubmed |
| pubmed-article:15292211 | pubmed:affiliation | Institut de Neurobiologie Alfred Fessard, IFR 2118 CNRS, Laboratoire de Neurobiologie Cellulaire et Moléculaire, UPR 9040 CNRS, B?timent 33, 1 avenue de la terrasse 91198 Gif sur Yvette, France. Elisabeth.Traiffort@nbcm.cnrs-gif.fr | lld:pubmed |
| pubmed-article:15292211 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:15292211 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| entrez-gene:6469 | entrezgene:pubmed | pubmed-article:15292211 | lld:entrezgene |
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