Item type:Thesis, Open Access

Punktmutationsanalysen bei GLI3-assoziierten Krankheitsbildern: Greig Cephalopolysyndaktylie-Syndrom, Pallister-Hall-Syndrom und isolierte Polydaktylien

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2006-05-24

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Philipps-Universität Marburg
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Abstract

For the formation of the extremities, multiple genes are responsible. The Sonic Hedgehog-Patched-GLI Signal transduction cascade plays a key role in the development of the anterior-posterior polarity of the extremities (SHH-PTCH-GLI signal cascade). Dysmorphogenetic disorders of the extremities occurs regularly, but nut exclusively in the case of deregulation of one of these factors, e.g. by mutations. Among these disorders are GLI-3 associated morphopathies of the extremities, which have been analyzed in this work. Here, several point mutations have been detected in the human gene of GLI3 (7p13), a transcription factor containing several zinc-finger motifs. Actually, four autosomal-dominant inherited malformation-syndromes have been associated with GLI3-mutations: 1. Greig Cephalopolysyndactily-Syndrome (GCPS) 2. Pallister-Hall-Syndrome (PHS) 3. Post-axial Polydactily Type A (PAP-A) 4. Pre-axial Polydactily Type IV (PPD-IV) Due to this work, the case numbers of GLI3 associated morphopathies have been increased. Standard methods like the non-radioactive single-strand conformation analysis as well as sequencing have been used. Altogether 12 mutations in patients with a clinically diagnosed GCPS, 2 mutations in a patient with clinically confirmed PHS, as well as 2 further mutations in patients with PPD-IV have been identified. In detail, 9 mutations affected the N-terminus or the central zinc-finger motif of the DNA binding domain of the GLI3 transcription factor. Further 7 mutations affected the C-terminal part of the protein. The new case numbers identified here, increase and complete the known spectrum of GLI3 mutations. The molecular consequences of these mutations, possible genotype-phenotype correlations and mutation-hotspots are discussed in this work.

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Dates
Created: 2005Issued: 2006-05-24Updated: 2011-08-10
DOI
https://doi.org/10.17192/z2006.0306
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
Sonic-HedgehogSonic-HedgehogGreig-Cephalopolysyndaktylie Syndrom (GCPS)SSCAPallister Hall SyndromSHHSSCAPostaxiale PolydaktylieGLI3GLI3Greig-Cephalopolysyndaktylie Syndrom (GCPS)SHHPostaxiale PolydaktyliePallister Hall Syndrom
DFG-subjects
GenotypNonsensmutationDNSGenmutationPunktmutationSignaltransduktionTranskriptionsfaktor
DDC-Numbers
610
License
https://rightsstatements.org/vocab/InC-NC/1.0/
URI
https://open.uni-marburg.de/handle/10.17192/z2006.0306
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Driess, Stephanie: Punktmutationsanalysen bei GLI3-assoziierten Krankheitsbildern: Greig Cephalopolysyndaktylie-Syndrom, Pallister-Hall-Syndrom und isolierte Polydaktylien. : Philipps-Universität Marburg 2006-05-24. DOI: https://doi.org/10.17192/z2006.0306.

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