Assessment of the structural and functional impact of in-frame mutations of the DMD gene, using the tools included in the eDystrophin online database.
Background: Dystrophin is a large essential protein of skeletal and heart muscle. It is a filamentous scaffolding protein with numerous binding domains. Mutations in the DMD gene, which encodes dystrophin, mostly result in the deletion of one or several exons and cause Duchenne (DMD) and Becker (BMD...
| Publicado en: | Orphanet Journal of Rare Diseases Vol. 7; no. 1; pp. 45 - 46 |
|---|---|
| Autores principales: | , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
BioMed Central
2012
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104371742&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104371742 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 17501172 38NP jtl: Orphanet Journal of Rare Diseases issn: 17501172 maglogo: N pubinfo: dt: 2012 vid: 7 iid: 1 pid: 24147 pub: BioMed Central artinfo: ui: 104371742 104371742 NLM22776072 2011700425 10.1186/1750-1172-7-42 NLM22776072 104371742 ppf: 45 ppct: 1 formats: tig: atl: Assessment of the structural and functional impact of in-frame mutations of the DMD gene, using the tools included in the eDystrophin online database. aug: au: Nicolas, Aurélie Lucchetti-Miganeh, Céline Yaou, Rabah Ben Kaplan, Jean-Claude Chelly, Jamel Leturcq, France Barloy-Hubler, Frédérique Le Rumeur, Elisabeth affil: Université de Rennes 1, Rennes, France. elisabeth.lerumeur@univ-rennes1.fr. sug: subj: Muscle Proteins Genetic Techniques Muscular Dystrophy, Duchenne Mutation Genes Adolescence Bioinformatics Resource Databases Female Genotype Human Internet Male Muscular Dystrophy, Duchenne Pathology Adolescent: 13-18 years Female Male ab: Background: Dystrophin is a large essential protein of skeletal and heart muscle. It is a filamentous scaffolding protein with numerous binding domains. Mutations in the DMD gene, which encodes dystrophin, mostly result in the deletion of one or several exons and cause Duchenne (DMD) and Becker (BMD) muscular dystrophies. The most common DMD mutations are frameshift mutations resulting in an absence of dystrophin from tissues. In-frame DMD mutations are less frequent and result in a protein with partial wild-type dystrophin function. The aim of this study was to highlight structural and functional modifications of dystrophin caused by in-frame mutations.Methods and Results: We developed a dedicated database for dystrophin, the eDystrophin database. It contains 209 different non frame-shifting mutations found in 945 patients from a French cohort and previous studies. Bioinformatics tools provide models of the three-dimensional structure of the protein at deletion sites, making it possible to determine whether the mutated protein retains the typical filamentous structure of dystrophin. An analysis of the structure of mutated dystrophin molecules showed that hybrid repeats were reconstituted at the deletion site in some cases. These hybrid repeats harbored the typical triple coiled-coil structure of native repeats, which may be correlated with better function in muscle cells.Conclusion: This new database focuses on the dystrophin protein and its modification due to in-frame deletions in BMD patients. The observation of hybrid repeat reconstitution in some cases provides insight into phenotype-genotype correlations in dystrophin diseases and possible strategies for gene therapy. The eDystrophin database is freely available: http://edystrophin.genouest.org/. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|