Mutation analysis of TRPS1 gene including core promoter, 5'UTR, and 3'UTR regulatory sequences with insight into their organization
Language English Country Netherlands Media print-electronic
Document type Journal Article
PubMed
27826100
DOI
10.1016/j.cca.2016.11.007
PII: S0009-8981(16)30453-3
Knihovny.cz E-resources
- Keywords
- Alternative splicing, Chromosomal rearrangement, Mutation, NGS, Promoter,
- MeSH
- 3' Untranslated Regions genetics MeSH
- 5' Untranslated Regions genetics MeSH
- Child MeSH
- DNA-Binding Proteins chemistry genetics MeSH
- Adult MeSH
- Haploinsufficiency MeSH
- Langer-Giedion Syndrome genetics MeSH
- Humans MeSH
- Young Adult MeSH
- DNA Mutational Analysis * MeSH
- Child, Preschool MeSH
- Promoter Regions, Genetic genetics MeSH
- Repressor Proteins MeSH
- Amino Acid Sequence MeSH
- Base Sequence MeSH
- Transcription Factors chemistry genetics MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- 3' Untranslated Regions MeSH
- 5' Untranslated Regions MeSH
- DNA-Binding Proteins MeSH
- Repressor Proteins MeSH
- Transcription Factors MeSH
- TRPS1 protein, human MeSH Browser
The TRPS1 protein is a potent regulator of proliferation, differentiation, and apoptosis. The TRPS1 gene aberrations are strongly associated with rare trichorhinophalangeal syndrome (TRPS) development. We have conducted MLPA analysis to capture deletion within the crucial 8q24.1 chromosomal region in combination with mutation analysis of TRPS1 gene including core promoter, 5'UTR, and 3'UTR sequences in nine TRPS patients. Low complexity or extent of untranslated regulatory sequences avoided them from analysis in previous studies. Amplicon based next generation sequencing used in our study bridge over these technical limitations. Finally, we have made extended in silico analysis of TRPS1 gene regulatory sequences organization. Single contiguous deletion and an intragenic deletion intervening several exons were detected. Mutation analysis revealed five TRPS1 gene aberrations (two structural rearrangements, two nonsense mutations, and one missense substitution) reaching the overall detection rate of 78%. Several polymorphic variants were detected within the analysed regulatory sequences but without proposed pathogenic effect. In silico analysis suggested alternative promoter usage and diverse expression effectivity for different TRPS1 transcripts. Haploinsufficiency of TRPS1 gene was responsible for most of the TRPS phenotype. Structure of TRPS1 gene regulatory sequences is indicative of generally low single allele expression and its tight control.
Department of Medical Genetics University Hospital Brno Cernopolni 212 9 625 00 Brno Czech Republic
Genetika Ostrava s r o Korenskeho 1317 12 702 00 Ostrava Czech Republic
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