33 documents found, page 1 of 4
A genetic interaction of NRXN2 with GABRE, SYT1 and CASK in migraine patients: ...
Alves-Ferreira, M; Quintas, M; Sequeiros, J; Sousa, A; Pereira-Monteiro, J; Alonso, I; Neto, JL; Lemos, CBackground: Migraine is a multifactorial disorder that is more frequent (two to four times) in women than in men. In recent years, our research group has focused on the role of neurotransmitter release and its regulation. Neurexin (NRXN2) is one of the components of the synaptic vesicle machinery, responsible for connecting intracellular fusion proteins and synaptic vesicles. Our aim was to continue exploring t...
Beyond Val30Met transthyretin (TTR): variants associated with age-at-onset in h...
Alves-Ferreira, M; Azevedo, A; Coelho, T; Santos, D; Sequeiros, J; Alonso, I; Sousa, A; Lemos, CObjectives: Val30Met in transthyretin (TTR) gene is causative for familial amyloid polyneuropathy (FAP). FAP shows a wide variation in age-at-onset (AO) between clusters, families, and among generations. We aim at identifying genetic modifiers of disease onset that may contribute to this variability in Portuguese patients by identifying other variants in TTR locus, beyond the TTR-FAP causing variant that could ...
Novel mag variant causes cerebellar ataxia with oculomotor apraxia: Molecular b...
Santos, M; Damásio, J; Kun-Rodrigues, C; Barbot, C; Sequeiros, J; Brás, J; Alonso, I; Guerreiro, RHomozygous variants in MAG, encoding myelin-associated glycoprotein (MAG), have been associated with complicated forms of hereditary spastic paraplegia (HSP). MAG is a glycoprotein member of the immunoglobulin superfamily, expressed by myelination cells. In this study, we identified a novel homozygous missense variant in MAG (c.124T>C; p.Cys42Arg) in a Portuguese family with early-onset autosomal recessive cere...
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...
Genome-wide association study identifies genetic factors that modify age at ons...
Akçimen, F; Martins, S; Liao, C; Bourassa, CV; Catoire, H; Nicholson, GA; Riess, O; Raposo, M; França, MC; Vasconcelos, J; Lima, M; Lopes-Cendes, IMachado-Joseph disease (MJD/SCA3) is the most common form of dominantly inherited ataxia worldwide. The disorder is caused by an expanded CAG repeat in the ATXN3 gene. Past studies have revealed that the length of the expansion partly explains the disease age at onset (AO) variability of MJD, which is confirmed in this study (Pearson's correlation coefficient R2 = 0.62). Using a total of 786 MJD patients from f...
Is the high frequency of machado-joseph disease in China due to new mutational ...
Li, T; Martins, S; Peng, Y; Wang, P; Hou, X; Chen, Z; Wang, C; Tang, Z; Qiu, R; Chen, C; Hu, Z; Xia, K; Tang, B; Sequeiros, J; Jiang, HMachado-Joseph disease (MJD, also known as spinocerebellar ataxia 3 or SCA3) is the most common dominant ataxia worldwide, with an overall average prevalence of 1-5/100,000. To this date, two major ancestral lineages have been found throughout the world. In China, the relative frequency of MJD among the SCAs reaches as high as 63%, however, little is known about its mutational origin in this country. We analyze...
Large Normal Alleles of ATXN2 Decrease Age at Onset in Transthyretin Familial A...
Santos, D; Coelho, T; Alves-Ferreira, M; Sequeiros, J; Mendonça, D; Alonso, I; Sousa, A; Lemos, CObjective: Transthyretin (TTR)-related familial amyloid polyneuropathy (FAP) is an autosomal dominant neurological disease, caused most frequently by a Val30Met (now classified as Val50Met) substitution in TTR. Age at onset (AO) ranges from 19 to 82 years, and variability exists mostly between generations. Unstable oligonucleotide repeats in various genes are the mechanism behind several neurological diseases, ...
C1QA and C1QC modify age-at-onset in familial amyloid polyneuropathy patients
Dias, A; Santos, D; Coelho, T; Alves-Ferreira, M; Sequeiros, J; Alonso, I; Sousa, A; Lemos, CObjectives: Transthyretin (TTR) familial amyloid polyneuropathy (FAP) (OMIM 176300) shows a variable age-at-onset (AO), including within families. We hypothesized that variants in C1QA and C1QC genes, might also act as genetic modifiers of AO in TTR-FAP Val30Met Portuguese patients. Methods: We analyzed DNA samples of 267 patients (117 families). To search for variants, all exons and flanking regions were genot...
Parkin truncating variants result in a loss-of-function phenotype
Santos, M; Morais, S; Pereira, C; Sequeiros, J; Alonso, IParkinson disease (PD) is the second most common neurodegenerative disorder. Most cases of PD are sporadic, while 5–10% have a known genetic basis. Variants in the PARK2 gene are the most frequent cause of autosomal recessive juvenile-onset PD. PARK2 encodes parkin, a multi-domain protein that functions as an ubiquitin E3 ligase. Numerous variants spanning all parkin domains have been identified, although the p...
A pipeline to assess disease-associated haplotypes in repeat expansion disorder...
Costa, IPD; Almeida, B; Sequeiros, J; Amorim, A; Martins, SAt least 40 human diseases are associated with repeat expansions; yet, the mutational origin and instability mechanisms remain unknown for most of them. Previously, genetic epidemiology and predisposing backgrounds for the instability of some expanding loci have been studied in different populations through the analysis of diversity flanking the respective pathogenic repeats. Here, we aimed at developing a pipe...