Browsing by Author "Pinto, Maximina"
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- Co-segregation of trichorhinophalangeal syndrome with a t(8;13)(q23.3;q21.31) familial translocation that appears to increase TRPS1 gene expressionPublication . David, Dezső; Marques, Bárbara; Ferreira, Cristina; Araújo, Carlos; Vieira, Luís; Soares, Gabriela; Dias, Cristina; Pinto, MaximinaTrichorhinophalangeal syndrome type I (TRPS I) is a rare autosomal dominant syndrome caused by haploinsufficiency of TRPS1 due to point mutations or deletions. Here we report the first familial TRPS I due to a t(8;13)(q23.3;q21.31) translocation breakpoint <100 kb from the 5’ end of TRPS1. Based on the additional abnormalities observed exclusively in the index patient that are mainly compatible with clinical features of TRPS, her phenotype was defined as expanded TRPS I including brain malformations and intellectual disability. Initial analyses did not reveal any genetic defect affecting TRPS1 or any genomic alteration within the breakpoint regions or elsewhere in the genome. The pathogenic chromosome 8q23.3 breakpoint is at position g.116,768,309_116,768,310 within a transposon type I element, 87 kb from the TRPS1 5’ end. The 13q21.31 breakpoint is within a tandem repeat region at position g.65,101,509_65,101,510 (genome assembly GRCh37/hg19). This breakpoint is flanked by protocadherin 9 (PCDH9) and protocadherin 20 (PCDH20). As an outcome of the translocation, an evolutionarily conserved non-coding VISTA enhancer element from 13q21.31 is placed within the TRPS1 5’ region, 1,294 bp from the breakpoint. The increased expression of TRPS1 found by three independent methods is most probably translocation allele derived and driven by the translocated enhancer element. The index patient’s expanded phenotype presumably involves the epithelial-to-mesenchymal transition pathway that may be due to TRPS1 overexpression. Together, these findings support that the reported translocation associated phenotypes are “cis-ruption” and TRPS1 overexpression related, the latter most probably caused by the novel enhancer element in the TRPS1 5’ region.
- Programa Nacional de Diagnóstico Precoce. Centro de Diagnóstico Pré-natal: relatório de actividades em 1987Publication . Osório, Rui Vaz; Pinto, MaximinaRelatório de actividades desenvolvidas pelo Programa Nacional de Diagnóstico Precoce e o Centro de Diagnóstico Pré-natal no ano de 1987.
- Programa Nacional de Diagnóstico Precoce. Centro de Diagnóstico Pré-natal: relatório de actividades em 1988Publication . Osório, Rui Vaz; Pinto, MaximinaRelatório de actividades desenvolvidas pelo Programa Nacional de Diagnóstico Precoce e o Centro de Diagnóstico Pré-natal no ano de 1988.
- Programa Nacional de Diagnóstico Precoce. Centro de Diagnóstico Pré-natal: relatório de actividades em 1989Publication . Osório, Rui Vaz; Pinto, MaximinaRelatório de actividades desenvolvidas pelo Programa Nacional de Diagnóstico Precoce e o Centro de Diagnóstico Pré-natal no ano de 1989.
- Programa Nacional de Diagnóstico Precoce. Centro de Diagnóstico Pré-natal: relatório de actividades em 1990Publication . Osório, Rui Vaz; Pinto, MaximinaRelatório de actividades desenvolvidas pelo Programa Nacional de Diagnóstico Precoce e o Centro de Diagnóstico Pré-natal no ano de 1990.
- Programa Nacional de Diagnóstico Precoce. Centro de Diagnóstico Pré-natal: relatório de actividades em 1991Publication . Osório, Rui Vaz; Pinto, MaximinaRelatório de actividades desenvolvidas pelo Programa Nacional de Diagnóstico Precoce e o Centro de Diagnóstico Pré-natal no ano de 1991.
- Tricho-rhino-phalangeal syndrome type I as a “cis-ruption disorder” caused by a translocationPublication . Marques, Bárbara; Ferreira, Cristina; Araújo, Carlos; Vieira, Luís; Martins, Márcia; Pinto, Maximina; Dias, Cristina; David, DezsőTricho-rhino-phalangeal syndrome type I (TRPS I; OMIM 190350) and type II (OMIM 150230) are two forms of the rare autosomal-dominant TRP malformation syndrome localised in 8q23.3–24.1. TRPS I is generally caused by point mutations or deletions of the TRPS1 gene, whereas type II is characterised by the presence of multiple cartilage exostoses (EXT) and deletions comprising the TRPS1 and EXT1 genes. In the present study, we have mapped and sequenced the breakpoints of a balanced familial translocation [t(8;13)(q23.3;q21.32)] segregating with mild TRPS I and analysed the TRPS1 candidate gene. The proband, in addition to features compatible with TRPS I, also presented developmental delay and severe mental retardation. The pathogenic chromosome 8 breakpoint was localised within a transposon type I element at 116.768 Mb, 87 kb from the TRPS1 5′ end. The breakpoint on chromosome 13 was localised within a gene-poor region at 65.101 Mb, and the nearest gene, 1.5 Mb distal from the breakpoint, is protocadherin 9 (PCDH9). Analysis of the three affected relatives by the 33K tiling BAC array and of the proband by 2.7-M high-resolution oligonucleotide array painting did not reveal additional genomic variation. Furthermore, mutation screening of the TRPS1 also did not reveal any alteration. Finally, expression studies of TRPS1 performed from LCLs indicate that inter-individual variation is higher than the expected gene expression changes induced by the translocation. Although the reason underlying the severe mental retardation observed in the proband is unknown, the available data indicate that this is not associated with the translocation. As far as we know, this is the first reported case of position effect or “cis-ruption” causing TRPS I. Finally, further studies are necessary to unveil the molecular pathogenic mechanisms of this “cis-ruption disorder” triggered by chromosometranslocation.