Teste Repositóri
2014-01-01
Resultados de pesquisa
Foram encontrados 9 registos.
Publicado em: Molecular Genetics and Metabolism 105 (2012) S15–S69. Disponível em: http://www.sciencedirect.com/science/article/pii/S1096719211004343
Abstract
The main clinical features of two siblings from a consanguineous marriage were progressive myoclonic epilepsy without intellectual impairment and a nephrotic syndrome with a strong accumulation of C1q in capillary loops and mesangium of kidney. The biochemical analysis of one of the patients revealed a normal beta-glucocerebrosidase activity in leukocytes, but a severe enzymatic deficiency in cultured skin fibroblasts. This deficiency suggested a defect in the intracellular sorting pathway of this enzyme. The sequence analysis of the gene encoding LIMP-2 (SCARB2), the sorting receptor for beta-glucocerebrosidase, confirmed this hypothesis. A homozygous nonsense mutation in codon 178 of SCARB2 was found in the patient, whereas her healthy parents were heterozygous for the mutation. Besides lacking immunodetectable LIMP-2, pati...
Background: Evidences from animal models have demonstrated that depletion of brain serotonin (5-HT), a neurotransmitter with a pivotal role in neurodevelopment and brain plasticity, lowers the threshold to induced seizures. It was also demonstrated that anti-epileptic drugs increase endogenous 5-HT concentrations and that 5HT-1B receptors could have an anticonvulsant role. Association studies have demonstrated that a polymorphism (rs6296) in 5HTR-1B gene may be a susceptibility factor for with temporal lobe epilepsy (TLE) development. The rs6296 G allele has been associated with decreased receptor activity. Our aim was to analyse the association between rs6296 and the development and clinical features of Mesial Temporal Lobe Epilepsy (MTLE) in a Portuguese population.
Material and methods: A cohort of 121 MTLE patients (67 F, 54 M, ...
Unverricht-Lundborg disease (ULD) is the most common form of progressive myoclonic epilepsy worldwide. It is an autosomal recessive neurodegenerative disorder caused by mutations in the cystatin B gene (CSTB) that
encodes an inhibitor of several lysosomal cathepsins. An unstable expansion, missense, nonsense, frameshift and mutations that may lead to alternative splicing have been described as causal of ULD.
Recently, our group described an ULD patient who is homozygous for a new synonymous mutation (c.66G>A; p.Q22Q) located at the last nucleotide of exon 1. The transcriptional profile analysis allowed the identification of two CSTB splice variants, one of normal size with the G>A change and other with partial inclusion of intron
1 due to activation of a cryptic splice-site inside the intronic sequence.
To correct the splice defect...
Purpose: Evidences from animal models have demonstrated that depletion
of brain serotonin (5-HT), a neurotransmitter with a pivotal role in
neurodevelopment and brain plasticity, lowers the threshold to induced
seizures. It was also demonstrated that anti-epileptic drugs increase
endogenous 5-HT concentrations. Studies in brain tissue from Mesial
Temporal lobe Epilepsy (MTLE) patients have showed that serotonin
type 2a receptor (HTR2A) is downregulated in these patients. HTR2A
expression levels may be modulated by a 102 T>C polymorphism. The
aim of this study was to analyse the association between 102T>C polymorphism
and the development and clinical features of MTLE-HS in a
Portuguese population.
Methods: A cohort of 112 MTLE-HS patients (62F, 50M, mean
age = 44 11 years, age of onset = 13 9 years, 97 patients with
dru...
Purpose: Apolipoprotein E (ApoE) is the main lipoprotein secreted in
brain. It has a critical immuno-modulatory function, influences neurotransmission
and is involved in repairing damaged neurons. ApoE e4
allele is an isoform of ApoE with altered protein function previously
associated with refractoriness and early onset epilepsy. Our purpose was
to investigate if apoE isoforms are risk factors for partial epilepsy and to
correlate genotypes with anti-epileptic drug response.
Methods: A cohort of 230 epileptic patients with partial epilepsies from
the outpatient clinic at HSA-CHP [109F, 121M; mean
age = 44 13 years, age of onset = 15 13 years; 168 patients with
Drug Refractory Epilepsy (DRE)] was compared with a cohort of 301
healthy individuals (HI) in a case control study. ApoE isoforms were
genotype by RFLP-PCR method...
Purpose: Human Herpesvirus 6 (HHV-6) is a ubiquitous virus acquired
mainly during the first 2 years of life. Mesial Temporal Lobe Epilepsy
with Hippocampal Sclerosis (MTLE-HS) is the most frequent pharmacoresistant
epilepsy. One of the most common antecedents of MTLE-HS is
febrile seizures (FS). Although the aetiology of MTLE-HS remains
unclear, evidences suggest that HHV-6 infection could be implicated.
The objective of this study was to investigate the presence of HHV-6B
DNA in the hippocampus and adjoining temporal cortex of MTLE-HS
patients submitted to surgery.
Methods: A total of 22 MTLE-HS (13 females and nine males) cases
were studied. The mean age at surgery was 39 9 years and mean age
at onset of seizures was 10 6 years. These study cohort was compared
to a group of 10 epileptic patients without MTLE-HS (six f...
Background: Adenosine is a ubiquitous homeostatic molecule that acts as an “endogenous neuromodulator”. Adenosine attenuates neuronal activity either presynaptically by inhibiting neurotransmitter release or by controlling neurotransmitter responsiveness at post-synaptic sites. Unbalanced adenosine metabolism has been implicated in pathological conditions such as epilepsy. Adenosine kinase (ADK), synthetized by astrocytes, is the key regulator of extracellular adenosine levels in the brain. Evidences from experimental studies support a role for ADK in brain injury associated with astrogliosis, a morphological hallmark of Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (MTLE-HS). In fact, expression of astrocytic ADK was found to be increased in the hippocampus and temporal cortex of MTLE-HS patients. Overexpression of ADK decr...
Epilepsy comprises several syndromes, amongst the most common being mesial temporal lobe epilepsy with hippocampal sclerosis. Seizures in mesial temporal lobe epilepsy with hippocampal sclerosis are typically drug-resistant, and mesial temporal lobe epilepsy with hippocampal sclerosis is frequently associated with important co-morbidities, mandating the search for better understanding and treatment. The cause of mesial temporal lobe epilepsy with hippocampal sclerosis is unknown, but there is an association with childhood febrile seizures. Several rarer epilepsies featuring febrile seizures are caused by mutations in SCN1A, which encodes a brain-expressed sodium channel subunit targeted by many anti-epileptic drugs. We undertook a genome-wide association study in 1018 people with mesial temporal lobe epilepsy with hippocampal sclerosis...
