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články
články
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Source: BMČ - články
Title
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,
Author
Solc, Roman
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.

Klugerova, Michaela
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.

Vcelak, Josef
Department of Molecular Endocrinology, Institute of Endocrinology, Narodni 8, 116 94 Prague, Czech Republic. Electronic address: jvcelak@endo.cz.

Baxová, Alice
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.

Kuklik, Miloslav
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.

Vseticka, Jan
Genetika Ostrava s.r.o., Korenskeho 1317/12, 702 00 Ostrava, Czech Republic. Electronic address: jan.vseticka55@gmail.com.

Beharka, Rastislav
Department of Medical Genetics, University Hospital Brno, Cernopolni 212/9, 625 00 Brno, Czech Republic. Electronic address: rbeharka@fnbrno.cz.

Hirschfeldova, Katerina
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.

Cited source
Clinica chimica acta. 2017, roč. 464, č. -, s. 30-36. ISSN: 0009-8981; 1873-3492 (elektronická verze).
Date of issue
2017
Language
angličtina
Country
Nizozemsko
Document type
články
DOI
Pubmed ID
Link
Record number
bmc17013414
Persistent link
English Abstract
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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