9 documents found, page 1 of 1
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 ...
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...
A Trans-acting Factor May Modify Age at Onset in Familial Amyloid Polyneuropath...
Alves-Ferreira, M; Coelho, T; Santos, D; Sequeiros, J; Alonso, I; Sousa, A; Lemos, CAlthough all familial amyloid polyneuropathy (FAP) ATTRV30M patients carry the same causative mutation, early (<40) and late-onset forms (≥50 years) of FAP may coexist in the same family. However, this variability in age at onset is still unexplained. To identify modifiers closely linked to the TTR locus that may in part be associated with age at onset of FAP ATTRV30M, in particular in a group of very early-ons...
mtDNA copy number associated with age of onset in familial amyloid polyneuropathy
Santos, D; Santos, MJ; Alves-Ferreira, M; Coelho, T; Sequeiros, J; Alonso, I; Oliveira, P; Sousa, A; Lemos, C; Grazina, Mbackground Transthyretin-related familial amyloid polyneuropathy (TTR-Fap Val30Met) shows a wide variation in age-at-onset (aO) between generations and genders, as in portuguese families, where women display a later onset and a larger anticipation (>10 years). Mitochondrial DNa (mtDNa) copy number was assessed to clarify whether it has a modifier effect on aO variability in portuguese patients. Methods The mtDN...
Variants in RBP4 and AR genes modulate age at onset in familial amyloid polyneu...
Santos, D; Coelho, T; Alves-Ferreira, M; Sequeiros, J; Mendonça, D; Alonso, I; Lemos, C; Sousa, AFamilial amyloid polyneuropathy (FAP) ATTRV30M is a neurodegenerative disorder due to point mutations in the transthyretin gene, with V30M being the commonest. FAP ATTRV30M shows a wide variation in age at onset (AO) between clusters, families and generations. Portuguese patients also show remarkable AO differences between genders. Genes found to be associated with FAP ATTRV30M pathways may act as AO modifiers....
Familial amyloid polyneuropathy in Portugal: New genes modulating age-at-onset
Santos, D; Coelho, T; Alves-Ferreira, M; Sequeiros, J; Mendonça, D; Alonso, I; Lemos, C; Sousa, AOBJECTIVES: Familial amyloid polyneuropathy (FAP ATTRV30M) shows a wide variation in age-at-onset (AO) between clusters, families, and among generations. We will now explore some candidate genes involved in altered disease pathways in order to assess their role as genetic modifiers of AO, using a family-centered approach. METHODS: We analyzed 62 tagging SNPs from nine genes-NGAL,MMP-9,BGN,MEK1,MEK2,ERK1,ERK2,HS...
Overcoming artefact: anticipation in 284 Portuguese kindreds with familial amyl...
Lemos, C; Coelho, T; Alves-Ferreira, M; Martins-da-Silva, A; Sequeiros, J; Mendonca, DBackground: Early-onset (≤40 years) and later-onset (≥50 years) cases of familial amyloid polyneuropathy (FAP) ATTRV30M are not different entities, often coexisting in the same family, and showing anticipation (earlier age-at-onset (AO) in younger generations, usually associated with more severe phenotype). Historically, anticipation has been ascribed to ascertainment biases. Our aim was to study anticipation i...