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1.
Gene ; 613: 10-13, 2017 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-28257836

RESUMO

Nowadays, obesity is the greatest scourge worldwide, particularly for the developed countries and is a huge burden for the public health. Over the past decade, GWAS have revealed a number of genes associated with obesity. The fat mass and obesity associated (FTO) gene was the first one associated with obesity in a significant number of populations and recent meta-analysis studies confirm this association. FTO is a N-methyladenosine demethylase and in addition to the genetic association, its biological role in the regulation of body weight has been documented. Due to lack of replication regarding FTO association with obesity in the Greek adult population, we analyzed three SNPs, i.e. rs9939609, rs9930506 and rs3751812 in a cohort of 203 adults, comprising of 95 obese, 58 overweight and 50 control individuals. Analysis has shown a significant association for FTO (rs9930506; A/G) 'G' allele with obesity and a difference by 3.2 BMI units between the two homozygotes (AA versus GG). This association, which was detected for the first time in this population, suggests that FTO rs9930506 is a predisposition marker to obesity in the Greek adults, but the results should be taken cautiously due to the limitation of the relatively small sample size of the subjects.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Obesidade/genética , Sobrepeso/genética , Polimorfismo de Nucleotídeo Único , Idoso , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Feminino , Grécia/epidemiologia , Humanos , Masculino , Obesidade/epidemiologia , Sobrepeso/epidemiologia
2.
Mol Diagn Ther ; 21(2): 137-152, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27905021

RESUMO

Netherton syndrome (OMIM #256500) is a rare but severe autosomal recessive form of ichthyosis that affects the skin, hair, and immune system. The identification of SPINK5, which encodes for the serine protease inhibitor LEKTI, as the gene responsible for Netherton syndrome, enabled the search for causative mutations in Netherton syndrome patients and families. However, information regarding these mutations and their association with the pathological Netherton syndrome phenotype is scarce. Herein, we provide an up-to-date overview of 80 different mutations in exonic as well as intronic regions that have been currently identified in 172 homozygous or compound heterozygous patients from 144 families. Genotypes with mutations located more upstream in LEKTI correlate with more severe phenotypes compared with similar mutations located towards the 3' region. Furthermore, splicing mutations and post-transcriptional mechanism of nonsense-mediated mRNA decay affect LEKTI expression in variable ways. Genotype-phenotype correlations form the basis of prenatal diagnosis in families with a history of Netherton syndrome and when consanguinity is implied.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Síndrome de Netherton/diagnóstico , Síndrome de Netherton/genética , Fenótipo , Alelos , Humanos , Mutação , Proteínas Secretadas Inibidoras de Proteinases/genética , Inibidor de Serinopeptidase do Tipo Kazal 5
4.
Arthritis Res Ther ; 17: 63, 2015 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-25885039

RESUMO

INTRODUCTION: We have hypothesized that incompatibility between the G1m genotype of the patient and the G1m1 and G1m17 allotypes carried by infliximab (INX) and adalimumab (ADM) could decrease the efficacy of these anti-tumor necrosis factor (anti-TNF) antibodies in the treatment of rheumatoid arthritis (RA). METHODS: The G1m genotypes were analyzed in three collections of patients with RA totaling 1037 subjects. The first, used for discovery, comprised 215 Spanish patients. The second and third were successively used for replication. They included 429 British and Greek patients and 393 Spanish and British patients, respectively. Two outcomes were considered: change in the Disease Activity Score in 28 joint (ΔDAS28) and the European League Against Rheumatism (EULAR) response criteria. RESULTS: An association between less response to INX and incompatibility of the G1m1,17 allotype was found in the discovery collection at 6 months of treatment (P = 0.03). This association was confirmed in the replications (P = 0.02 and 0.08, respectively) leading to a global association (P = 0.001) that involved a mean difference in ΔDAS28 of 0.4 units between compatible and incompatible patients (2.3 ± 1.5 in compatible patients vs. 1.9 ± 1.5 in incompatible patients) and an increase in responders and decrease in non-responders according to the EULAR criteria (P = 0.03). A similar association was suggested for patients treated with ADM in the discovery collection, but it was not supported by replication. CONCLUSIONS: Our results suggest that G1m1,17 allotypes are associated with response to INX and could aid improved therapeutic targeting in RA.


Assuntos
Adalimumab/genética , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Imunoglobulina G/genética , Infliximab/genética , Adalimumab/uso terapêutico , Adulto , Antirreumáticos/uso terapêutico , Artrite Reumatoide/imunologia , Sequência de Bases , Feminino , Genótipo , Humanos , Alótipos de Imunoglobulina , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Polimorfismo de Nucleotídeo Único , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores
5.
Pharmacogenomics ; 16(4): 333-45, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25823782

RESUMO

OBJECTIVES: Reproducible association of a functional polymorphism in FCGR2A with response to a TNF inhibitor (TNFi) in patients with rheumatoid arthritis (RA) led us to explore other FcγR functional polymorphisms. METHODS: Functional polymorphisms FCGR3A F158V, FCGR2B I223T and promoter VNTR in FCGRT were analyzed in up to 429 patients with RA. Response to TNFi was recorded during standard care at 3, 6 and 12 months of follow-up. Fixed effects meta-analysis of studies addressing FCGR3A F158V polymorphism, which is the most studied of these polymorphisms, was conducted with inverse variance weighting. RESULTS: None of the functional polymorphisms were associated with change in DAS28. Meta-analysis of the seven studies (899 patients) with available data addressing association of FCGR3A F158V with response to TNFi in RA showed no association (OR: 1.11, 95% CI: 0.8-1.5; p = 0.5). CONCLUSION: None of the three functional polymorphisms in FcγR genes showed association with response to TNFi in patients with RA. These negative results were obtained in spite of the larger size of this study relative to previous studies addressing the same polymorphisms. In addition, meta-analysis of FCGR3A F158V was also negative against the results provided by previous studies. Original submitted 17 September 2014; Revision submitted 9 December 2014.


Assuntos
Artrite Reumatoide/genética , Antígenos de Histocompatibilidade Classe I/genética , Receptores Fc/genética , Receptores de IgG/genética , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Fator de Necrose Tumoral alfa/antagonistas & inibidores
6.
Arthritis Res Ther ; 16(2): R66, 2014 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-24612463

RESUMO

INTRODUCTION: In this study, our aim was to elucidate the role of four polymorphisms identified in a prior large genome-wide association study (GWAS) in which the investigators analyzed the responses of patients with rheumatoid arthritis (RA) to treatment with tumor necrosis factor inhibitors (TNFi). The authors of that study reported that the four genetic variants were significantly associated. However, none of the associations reached GWAS significance, and two subsequent studies failed to replicate these associations. METHODS: The four polymorphisms (rs12081765, rs1532269, rs17301249 and rs7305646) were genotyped in a total of 634 TNFi-treated RA patients of Spanish Caucasian origin. Four outcomes were evaluated: changes in the Disease Activity Score in 28 joints (DAS28) after 6 and 12 months of treatment and classification according to the European League Against Rheumatism (EULAR) response criteria at the same time points. Association with DAS28 changes was assessed by linear regression using an additive genetic model. Contingency tables of genotype and allele frequencies between EULAR responder and nonresponder patients were compared. In addition, we combined our data with those of previously reported studies in a meta-analysis including 2,998 RA patients. RESULTS: None of the four genetic variants showed an association with response to TNFi in any of the four outcomes analyzed in our Spanish patients. In addition, only rs1532269 yielded a suggestive association (P = 0.0033) with the response to TNFi when available data from previous studies were combined in the meta-analysis. CONCLUSION: Our data suggest that the rs12081765, rs1532269, rs17301249 and rs7305646 genetic variants do not have a role as genetic predictors of TNFi treatment outcomes.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Idoso , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
7.
Pharmacogenet Genomics ; 24(5): 238-45, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24667440

RESUMO

OBJECTIVES: We aimed to assess a functional polymorphism in FCGR2A H131R, for association with the treatment response to Fc-containing inhibitors of tumor necrosis factor (TNF). METHODS: A total of 429 biologic-naive patients with rheumatoid arthritis collected in two sets (299 and 130) were treated during standard care with infliximab (INX), etanercept, or adalimumab. Response to the treatment was evaluated at 3, 6, and 12 months of follow-up as the change in the Disease Activity Score (DAS) 28 from baseline and as the response by the European League Against Rheumatism (EULAR) criteria. These variables were analyzed for association with linear and logistic regression models that included sex, inhibitors of TNF, and baseline DAS28 as covariates. RESULTS: Significant association was found between the FCGR2A H131R polymorphism and the response to treatment with INX, but not with the other two TNF inhibitors. The 131R allele was associated with a lower change in DAS28 (P=0.04-0.008 at different times) in the first set of patients and confirmed in the second group of patients (P=0.026 at 3 months of follow-up). Association was also found in the comparison between nonresponders and responders to INX by the EULAR criteria. CONCLUSION: We found an association of the FCGR2A 131R allele with poor response to INX. This finding could be of utility to understand the mechanisms behind treatment failure and contribute to biomarker panels for INX response prediction.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Artrite Reumatoide/genética , Estudos de Associação Genética , Receptores de IgG/genética , Adalimumab , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Feminino , Humanos , Infliximab , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores
8.
Int J Environ Res Public Health ; 10(12): 6534-610, 2013 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-24317379

RESUMO

During the last three years Greece is experiencing the emergence of West Nile virus (WNV) epidemics. Within this framework, an integrated surveillance and control programme (MALWEST project) with thirteen associate partners was launched aiming to investigate the disease and suggest appropriate interventions. One out of seven work packages of the project is dedicated to the State of the Art report for WNV. Three expert working groups on humans, animals and mosquitoes were established. Medical databases (PubMed, Scopus) were searched together with websites: e.g., WHO, CDC, ECDC. In total, 1,092 relevant articles were initially identified and 258 of them were finally included as references regarding the current knowledge about WNV, along with 36 additional sources (conference papers, reports, book chapters). The review is divided in three sections according to the fields of interest: (1) WNV in humans (epidemiology, molecular characteristics, transmission, diagnosis, treatment, prevention, surveillance); (2) WNV in animals (epidemiological and transmission characteristics concerning birds, horses, reptiles and other animal species) and (3) WNV in mosquitoes (control, surveillance). Finally, some examples of integrated surveillance programmes are presented. The introduction and establishment of the disease in Greece and other European countries further emphasizes the need for thorough research and broadening of our knowledge on this viral pathogen.


Assuntos
Doenças das Aves/transmissão , Culicidae/virologia , Doenças dos Cavalos/transmissão , Répteis , Febre do Nilo Ocidental/transmissão , Animais , Doenças das Aves/epidemiologia , Aves , Grécia/epidemiologia , Doenças dos Cavalos/epidemiologia , Cavalos , Humanos , Vigilância da População , Febre do Nilo Ocidental/epidemiologia , Febre do Nilo Ocidental/prevenção & controle , Vírus do Nilo Ocidental/fisiologia
9.
PLoS One ; 8(5): e63901, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23691111

RESUMO

Infectious diseases of sheep are of major economic importance causing direct and indirect losses. Among the major sheep infectious agents are Small Ruminant Lentivirus, Chlamydophila abortus and Mycobacterium avium subsp. paratuberculosis infections, mainly due to their worldwide distribution and economic impact that they cause. Based on the differential susceptibility to infectious diseases between and within breeds and on the recent findings regarding the putative involvement of TLR9 in disease susceptibility, the aim of this study was to evaluate the levels of nucleotide variation of TLR9 and its mediator MyD88 in three sheep flocks originated from different breeds and assess their possible association with seropositivity/seronegativity for different infectious agents. The analysis indicated that the change of G to R at codon 520 of TLR9 polypeptide shows a significant association with Small Ruminant Lentivirus seropositivity. This amino-acid substitution, which can result in polarity change, might influence structure and function of LRR17, interfering with ligand binding and thus could be used in studies investigating susceptibility/resistance to Small Ruminant Lentivirus infections in sheep.


Assuntos
Lentivirus Ovinos-Caprinos/isolamento & purificação , Polimorfismo de Nucleotídeo Único , Ovinos/genética , Receptor Toll-Like 9/genética , Animais , Frequência do Gene , Heterozigoto , Dados de Sequência Molecular , Fator 88 de Diferenciação Mieloide/genética , Ovinos/classificação , Especificidade da Espécie
10.
Gene ; 512(2): 237-9, 2013 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-23103831

RESUMO

The prevalence of obesity has increased dramatically during the last thirty years in western countries with severe complications for health and economy. Obesity is the outcome of the strong interplay between genetic and environmental factors and is therefore widely expected that the discovery of the many genetic factors underlying the heritable risk of obesity will contribute critically to our basic knowledge of the disease etiopathogenesis and the identification of new targets for therapeutic intervention. The aim of the present study was to assess the genetic contribution of known polymorphisms in two genes that are linked to the pathogenetic mechanism of obesity. Analysis of vitamin D receptor (VDR) TaqI (rs731236; T/C) and fat mass and obesity-associated (FTO) (rs9939609; A/T) [corrected] polymorphisms in 82 obesity subjects and 102 controls showed significant association for VDR TaqI 'T' allele and obesity (OR: 2.07; 1.123-3.816; P=0.019), contributing to an elevated BMI of 3kg/m(2) per risk allele. No association was observed for the FTO polymorphism. These results further support a role for VDR as risk factor for obesity and suggest its further validation in larger independent populations as well as highlight a target for functional analysis towards therapeutic intervention in obese individuals.


Assuntos
Alelos , Obesidade/genética , Polimorfismo Genético , Receptores de Calcitriol/genética , Idoso , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Índice de Massa Corporal , Enzimas de Restrição do DNA , Feminino , Grécia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Prevalência , Proteínas/genética , Fatores de Risco
11.
Mol Diagn Ther ; 16(1): 29-34, 2012 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-22111980

RESUMO

BACKGROUND: Although biologic therapies have revolutionized the treatment of psoriasis, patients exhibit a substantial heterogeneous response that could be due to complex genetic heterogeneity. OBJECTIVE: The aim of this study was to investigate the possible influence of tumor necrosis factor-α (TNF), TNF receptor I (TNFRSF1A), and TNF receptor II (TNFRSF1B) gene polymorphisms on anti-TNF treatment responsiveness in psoriasis patients. METHODS: A Greek multicenter collaboration was established to recruit a cohort of patients (n = 80) with psoriasis treated with anti-TNF drugs. Single nucleotide polymorphisms (SNPs) in TNF (-238G>A, -308G>A, -857C>T), TNFRSF1A (36A>G), and TNFRSF1B (676T>G) were genotyped by PCR-restriction fragment length polymorphism assays. SNPs and haplotypes, including stratification by comorbidity status, were analyzed for association with treatment response after 6 months of therapy, defined as a reduction in the Psoriasis Area and Severity Index (PASI) score by >75% (responders) or ≤50% (nonresponders). RESULTS: Sixty-three patients (78.8%) were defined as responders (PASI score reduction >75%) and 17 patients (21.2%) were defined as nonresponders (PASI score reduction ≤50%). Carriage of TNF -857C or TNFRSF1B 676T alleles was associated with positive response to drug treatment in patients treated with etanercept (p = 0.002 and p = 0.001, respectively). None of the genotyped SNPs were associated with responsiveness to treatment with infliximab or adalimumab. Additionally, when patients were stratified by comorbidity status, none of the genotyped SNPs were alone associated with responsiveness to drug treatment. CONCLUSION: This study is the first in the field of psoriasis demonstrating a strong association between genetic markers and positive response to drug treatment. Validation of this result in larger studies, as well as analysis of other drug treatments, could provide the basis for individually tailored treatment, along with increased cost effectiveness and reduced unnecessary exposure to toxicity.


Assuntos
Polimorfismo de Nucleotídeo Único , Psoríase/tratamento farmacológico , Psoríase/genética , Receptores Tipo II do Fator de Necrose Tumoral/genética , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Fatores de Necrose Tumoral/genética , Adulto , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Genótipo , Grécia , Humanos , Infliximab , Masculino , Pessoa de Meia-Idade , Farmacogenética , Psoríase/imunologia , Psoríase/patologia , Estudos Retrospectivos , Fatores de Necrose Tumoral/imunologia
12.
Am J Med Genet A ; 155A(11): 2841-54, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21964744

RESUMO

We report on an intellectually disabled girl with a de novo satellited chromosome 10 (10qs) and performed a review of the literature of the non-acrocentric satellited chromosomes (NASC). Satellites and stalks normally occur on the short arms of acrocentric chromosomes; however, the literature cites several reports of satellited non-acrocentric chromosomes, which presumably result from a translocation with an acrocentric chromosome. This is, to our knowledge, the third report of a 10qs chromosome. The phenotype observed in the proband prompted a search for a structural rearrangement of chromosome 10q. By microsatellite analysis we observed a 4 Mb deletion on the long arm of chromosome 10, approximately 145 kb from the telomere. FISH and array CGH analyses revealed a complex rearrangement involving in range from the centromere to the telomere: A 9.64 Mb 10q26.11-q26.2 duplication, a 1.3 Mb region with no copy number change, followed by a 5.62 Mb 10q26.2-q26.3 deletion and a translocation of satellite material. The homology between the repeat sequences at 10q subtelomere region and the sequences on the acrocentric short arms may explain the origin of the rearrangement and it is likely that the submicroscopic microdeletion and microduplication are responsible for the abnormal phenotype in our patient. The patient presented here, with a 15-year follow-up, manifests a distinct phenotype different from the 10q26 pure distal monosomy and trisomy syndromes.


Assuntos
Deleção Cromossômica , Duplicação Cromossômica , Cromossomos Humanos Par 10/genética , Deficiência Intelectual/genética , Adolescente , Transtornos Dismórficos Corporais/genética , Transtornos Dismórficos Corporais/patologia , Centrômero/genética , Transtornos Cromossômicos/genética , Cromossomos Humanos Y/genética , Hibridização Genômica Comparativa , Feminino , Seguimentos , Humanos , Hibridização in Situ Fluorescente , Lactente , Padrões de Herança , Deficiência Intelectual/patologia , Região Organizadora do Nucléolo/genética , Fenótipo , Diagnóstico Pré-Natal , Telômero/genética , Translocação Genética
13.
Genet Test Mol Biomarkers ; 15(9): 613-7, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21473680

RESUMO

Impaired energy homeostasis and low-grade inflammation have been related to components of the metabolic syndrome (MetS) such as dyslipidemia, obesity, and insulin resistance. Single-nucleotide polymorphisms in the genes encoding for IL-6 (g.-634G>C; c.174G>C), TNFα (g.-308G>A), methylenetetrahydrofolate reductase (MTHFR) (c.677C>T), APOC3 (c.3175C>G), and APOA5 (g.-1131T>C) have been implicated in the processes of inflammation and energy intake that take place in the development of MetS manifestations. The aim of this study was to investigate the association between these polymorphisms and MetS, as defined by the National Cholesterol Education Program-Adult treatment Panel III criteria, in the Greek population. Overall, 30 unrelated subjects who met the criteria of MetS and 60 matched control subjects from central Greece were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. There was a significant association between both MTHFR c.677C>T (odds ratio: 4.02; confidence interval: 1.496-10.777; p=0.003) and APOA5 g.-1131T>C (odds ratio: 3.514; confidence interval: 1.065-11.585; p=0.035) and MetS. Analysis of constructed haplotypes showed a highly significant association between 677C-1131T-3175C haplotype and MetS (p<0.0001). Carriers of both MTHFR c.677T and APOA5 g.-1131C were associated with increased triglyceride levels (p=0.001 and p=0.003, respectively), compared with noncarriers. These results support a role for MTHFR and APOA5 as risk factors for MetS and suggest their further validation in larger independent populations.


Assuntos
Apolipoproteínas A/genética , Síndrome Metabólica/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Adulto , Apolipoproteína A-V , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genética Populacional , Genótipo , Grécia/epidemiologia , Humanos , Masculino , Síndrome Metabólica/epidemiologia , Polimorfismo de Nucleotídeo Único/fisiologia , Adulto Jovem
14.
Genomics ; 84(1): 69-81, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15203205

RESUMO

Fragile sites appear visually as nonstaining gaps on chromosomes that are inducible by specific cell culture conditions. Expansion of CGG/CCG repeats has been shown to be the molecular basis of all five folate-sensitive fragile sites characterized molecularly so far, i.e., FRAXA, FRAXE, FRAXF, FRA11B, and FRA16A. In the present study we have refined the localization of the FRA10A folate-sensitive fragile site by fluorescence in situ hybridization. Sequence analysis of a BAC clone spanning FRA10A identified a single, imperfect, but polymorphic CGG repeat that is part of a CpG island in the 5'UTR of a novel gene named FRA10AC1. The number of CGG repeats varied in the population from 8 to 13. Expansions exceeding 200 repeat units were methylated in all FRA10A fragile site carriers tested. The FRA10AC1 gene consists of 19 exons and is transcribed in the centromeric direction from the FRA10A repeat. The major transcript of approximately 1450 nt is ubiquitously expressed and codes for a highly conserved protein, FRA10AC1, of unknown function. Several splice variants leading to alternative 3' ends were identified (particularly in testis). These give rise to FRA10AC1 proteins with altered COOH-termini. Immunofluorescence analysis of full-length, recombinant EGFP-tagged FRA10AC1 protein showed that it was present exclusively in the nucleoplasm. We show that the expression of FRA10A, in parallel to the other cloned folate-sensitive fragile sites, is caused by an expansion and subsequent methylation of an unstable CGG trinucleotide repeat. Taking advantage of three cSNPs within the FRA10AC1 gene we demonstrate that one allele of the gene is not transcribed in a FRA10A carrier. Our data also suggest that in the heterozygous state FRA10A is likely a benign folate-sensitive fragile site.


Assuntos
Sítios Frágeis do Cromossomo/genética , Fragilidade Cromossômica/genética , Metilação de DNA , Proteínas Nucleares/genética , Expansão das Repetições de Trinucleotídeos/genética , Repetições de Trinucleotídeos/genética , Alelos , Processamento Alternativo/genética , Sequência de Aminoácidos , Humanos , Espaço Intranuclear/metabolismo , Dados de Sequência Molecular , Proteínas Nucleares/metabolismo , Especificidade de Órgãos/genética , Alinhamento de Sequência , Transcrição Genética/genética
15.
Hum Mol Genet ; 11(9): 1119-28, 2002 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-11978770

RESUMO

Autosomal dominant lateral temporal epilepsy (EPT; OMIM 600512) is a form of epilepsy characterized by partial seizures, usually preceded by auditory signs. The gene for this disorder has been mapped by linkage studies to chromosomal region 10q24. Here we show that mutations in the LGI1 gene segregate with EPT in two families affected by this disorder. Both mutations introduce premature stop codons and thus prevent the production of the full-length protein from the affected allele. By immunohistochemical studies, we demonstrate that the LGI1 protein, which contains several leucine-rich repeats, is expressed ubiquitously in the neuronal cell compartment of the brain. Moreover, we provide evidence for genetic heterogeneity within this disorder, since several other families with a phenotype consistent with this type of epilepsy lack mutations in the LGI1 gene.


Assuntos
Cromossomos Humanos Par 10/genética , Epilepsia do Lobo Temporal/genética , Mutação , Proteínas/genética , Processamento Alternativo , Sequência de Aminoácidos , Animais , Sequência de Bases , Northern Blotting , Encéfalo/citologia , Encéfalo/metabolismo , Primers do DNA/química , Feminino , Humanos , Técnicas Imunoenzimáticas , Masculino , Dados de Sequência Molecular , Linhagem , Coelhos , Sequências Repetitivas de Aminoácidos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência de Aminoácidos
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