9 documents found, page 1 of 1
Pentanucleotide repeat-related disorders: Genetics and bioinformatic discovery ...
Silveira, I; Bennett, MFIn recent years, a large group of familial epilepsies and hereditary ataxias have emerged, caused by an extraordinary type of a novel pentanucleotide repeat expansion that has arisen in a preexisting nonpathogenic repeat tract. Remarkably, these insertions have occurred in noncoding regions of genes expressed in the cerebellum, but with highly diverse functions. These conditions, clinically very heterogeneous, ...
Mutational mechanism for DAB1 (ATTTC) n insertion in SCA37: ATTTT repeat length...
Loureiro, JR; Oliveira, CL; Mota, C; Castro, AF; Costa, C; Loureiro, JL; Coutinho, P; Martins, S; Sequeiros, J; Silveira, IDynamic mutations by microsatellite instability are the molecular basis of a growing number of neuromuscular and neurodegenerative diseases. Repetitive stretches in the human genome may drive pathogenicity, either by expansion above a given threshold, or by insertion of abnormal tracts in nonpathogenic polymorphic repetitive regions, as is the case in spinocerebellar ataxia type 37 (SCA37). We have recently est...
Antisense transcription across nucleotide repeat expansions in neurodegenerativ...
Castro, AF; Loureiro, JR; Bessa, J; Silveira, IUnstable repeat expansions and insertions cause more than 30 neurodegenerative and neuromuscular diseases. Remarkably, bidirectional transcription of repeat expansions has been identified in at least 14 of these diseases. More remarkably, a growing number of studies has been showing that both sense and antisense repeat RNAs are able to dysregulate important cellular pathways, contributing together to the observ...
Mutational mechanism for DAB1 (ATTTC)n insertion in SCA37: ATTTT repeat lengthe...
Loureiro, JR; Oliveira, C; Mota, C; Castro, AF; Costa, C; Loureiro, J; Coutinho, P; Martins, S; Sequeiros, J; Silveira, IDynamic mutations by microsatellite instability are the molecular basis of a growing number of neuromuscular and neurodegenerative diseases. Repetitive stretches in the human genome may drive pathogenicity, either by expansion above a given threshold, or by insertion of abnormal tracts in nonpathogenic polymorphic repetitive regions, as is the case in spinocerebellar ataxia type 37 (SCA37). We have recently est...
A repeat-primed PCR assay for pentanucleotide repeat alleles in spinocerebellar...
Loureiro, JR; Oliveira, CL; Sequeiros, J; Silveira, ISpinocerebellar ataxia 37 (SCA37) is caused by an (ATTTC)n insertion in a polymorphic ATTTT repeat in the non-coding region of DAB1. The non-pathogenic alleles have a configuration [(ATTTT)7-400], whereas pathogenic alleles have a complex structure of [(ATTTT)60-79(ATTTC)31-75(ATTTT)58-90]. Molecular diagnosis of SCA37 is laborious because about 7% of the pentanucleotide repeat alleles in DAB1 are larger than 3...
A pentanucleotide ATTTC repeat insertion in the non-coding region of DAB1, mapp...
Seixas, AI; Loureiro, JR; Costa, C; Ordóñez-Ugalde, A; Marcelino, H; Oliveira, CL; Loureiro, JL; Dhingra, A; Brandão, E; Cruz, VT; Timóteo, AAdvances in human genetics in recent years have largely been driven by next-generation sequencing (NGS); however, the discovery of disease-related gene mutations has been biased toward the exome because the large and very repetitive regions that characterize the non-coding genome remain difficult to reach by that technology. For autosomal-dominant spinocerebellar ataxias (SCAs), 28 genes have been identified, b...
A novel H101Q mutation causes PKCgamma loss in spinocerebellar ataxia type 14
Alonso, I; Costa, C; Gomes, A; Ferro, A; Seixas, A; Silva, S; Cruz, V; Coutinho, P; Sequeiros, J; Silveira, ISpinocerebellar ataxia type 14 (SCA14) is an autosomal dominant neurodegenerative disorder, first described in a Japanese family, showing linkage to chromosome 19q13.4-qter. Recently, mutations have been identified in the PRKCG gene in families with SCA14. The PRKCG gene encodes the protein kinase Cgamma (PKCgamma), a member of a serine/threonine kinase family involved in signal transduction important for sever...
Trinucleotide repeats in 202 families with ataxia: a small expanded (CAG)n alle...
Silveira, I; Miranda, C; Guimarães, L; Moreira, MC; Alonso, I; Mendonça, P; Ferro, A; Pinto-Basto, J; Coelho, J; Ferreirinha, F; Poirier, JBACKGROUND: Ten neurodegenerative disorders characterized by spinocerebellar ataxia (SCA) are known to be caused by trinucleotide repeat (TNR) expansions. However, in some instances the molecular diagnosis is considered indeterminate because of the overlap between normal and affected allele ranges. In addition, the mechanism that generates expanded alleles is not completely understood. OBJECTIVE: To examine the...
Trinucleotide repeats in 202 families with ataxia: a small expanded (CAG)n alle...
Silveira, I; Miranda, C; Guimarães, L; Moreira, MC; Alonso, I; Mendonça, P; Ferro, A; Pinto-Basto, J; Coelho, J; Ferreirinha, F; Poirier, J; Vale, JBACKGROUND: Ten neurodegenerative disorders characterized by spinocerebellar ataxia (SCA) are known to be caused by trinucleotide repeat (TNR) expansions. However, in some instances the molecular diagnosis is considered indeterminate because of the overlap between normal and affected allele ranges. In addition, the mechanism that generates expanded alleles is not completely understood. OBJECTIVE: To examine the...