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Mutation analysis of TRPS1 gene including core promoter, 5'UTR, and 3'UTR regulatory sequences with insight into their organization
R. Solc, M. Klugerova, J. Vcelak, A. Baxova, M. Kuklik, J. Vseticka, R. Beharka, K. Hirschfeldova,
Language English Country Netherlands
Document type Journal Article
- 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
- 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
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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- $a Solc, Roman $u Department of Anthropology and Human Genetics, Faculty of Science, Charles University in Prague, Vinicna 7, 128 43 Prague, Czech Republic. Electronic address: roman.solc@natur.cuni.cz.
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- $a Mutation analysis of TRPS1 gene including core promoter, 5'UTR, and 3'UTR regulatory sequences with insight into their organization / $c R. Solc, M. Klugerova, J. Vcelak, A. Baxova, M. Kuklik, J. Vseticka, R. Beharka, K. Hirschfeldova,
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- $a 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.
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- $a Klugerova, Michaela $u Department of Anthropology and Human Genetics, Faculty of Science, Charles University in Prague, Vinicna 7, 128 43 Prague, Czech Republic. Electronic address: Mickey.007@seznam.cz.
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- $a Vcelak, Josef $u Department of Molecular Endocrinology, Institute of Endocrinology, Narodni 8, 116 94 Prague, Czech Republic. Electronic address: jvcelak@endo.cz.
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- $a Baxova, Alice $u Institute of Biology and Medical Genetics, 1st Faculty of Medicine and General University Hospital, Charles University in Prague, Albertov 4, 128 00 Prague, Czech Republic. Electronic address: baxova@vfn.cz.
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- $a Kuklik, Miloslav $u Department of Molecular Endocrinology, Institute of Endocrinology, Narodni 8, 116 94 Prague, Czech Republic; Genetic Department Olsanska, 1st and 3rd Faculty of Medicine, Charles University in Prague, Olsanska 2666/7, 130 00 Prague, Czech Republic. Electronic address: honza.kuklik@volny.cz.
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- $a Vseticka, Jan $u Genetika Ostrava s.r.o., Korenskeho 1317/12, 702 00 Ostrava, Czech Republic. Electronic address: jan.vseticka55@gmail.com.
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- $a Beharka, Rastislav $u Department of Medical Genetics, University Hospital Brno, Cernopolni 212/9, 625 00 Brno, Czech Republic. Electronic address: rbeharka@fnbrno.cz.
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- $a Hirschfeldova, Katerina $u Institute of Biology and Medical Genetics, 1st Faculty of Medicine and General University Hospital, Charles University in Prague, Albertov 4, 128 00 Prague, Czech Republic. Electronic address: khirs@lf1.cuni.cz.
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