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1.
Int J Immunogenet ; 50(4): 185-193, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37243939

RESUMO

Behçet's disease (BD) is a chronic auto inflammatory disorder of unknown aetiology. Recently, the dysregulation of interleukin-21 receptor (IL-21R) has been incriminated in different autoimmune and auto-inflammatory diseases, such as systemic lupus erythematous, rheumatoid arthritis, and type 1 diabetes. Herein, we aimed to investigate the association of two Il-21R gene polymorphisms with BD. IL-21R rs2214537 and IL-21R rs2285452 genotypings were investigated in a cohort of 110 adult patients with BD and 116 age and gender unmatched healthy controls. Genotyping was performed by mutagenically separated polymerase chain reaction with newly designed primers. IL-21R rs2285452 genotypes and alleles distribution were statistically different between patients with BD and controls. GA and AA genotypes carrying the minor A allele were more frequent in patients with BD than in healthy controls (37.3% and 11.8% vs. 23.3% and 3.4%, respectively). The minor A allele was associated with an increased BD risk (odds ratios = 2.42, 95% confidence interval = 1.214.87, p = .005). IL-21R rs2214537 GG genotype was found to be associated with susceptibility to BD in the recessive model (GG vs. CC + CG; p = .046, OR =  1.91, 95% CI =  1.003.650. IL-21R rs2285452 and IL-21R rs2214537 were not in linkage disequilibrium (D' = 0.42). The AG haplotype was more frequently observed in patients with BD than in controls (0.247 vs. 0.056, p =  .0001). This study for the first time reports the association of IL-21R rs2285452 and IL-21R rs2214537 with BD. Functional studies are required to elucidate the exact role of these genetic variants.


Assuntos
Síndrome de Behçet , Adulto , Humanos , Síndrome de Behçet/genética , Predisposição Genética para Doença , Frequência do Gene , Polimorfismo de Nucleotídeo Único , Genótipo
2.
J Hum Genet ; 60(1): 41-9, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25471516

RESUMO

The male genetic landscape of the territory currently known as Tunisia is hampered by the scarcity of data, especially from cosmopolitan areas such as the coastal city of Sousse. In order to alleviate this lacuna, 220 males from Sousse were examined, for the first time, for more than 50 Y-chromosome single-nucleotide polymorphisms (Y-SNPs) markers and compared with 3099 individuals from key geographically targeted locations in North Africa, Europe and the Near East. The paternal lineages observed belong to a common set of Y haplogroups previously described in North Africa. In addition to the prominent autochthonous North African E-M81 haplogroup which is exclusively represented by its subclade E-M183 (44.55% of Y-chromosomes), a number of Near Eastern Neolithic lineages including E-M78, J-M267 and J-M172 account for 39% of the Y-chromosomes detected. Principal component analysis based on haplogroup frequencies, multidimensional scaling based on Rst genetic distances and analyses of molecular variance using both Y-chromosome short tandem repeat haplotypes and Y-SNP haplogroup data revealed that the Tunisian and North African groups, as a whole, are intra- and inter-specific diverse with Sousse being highly heterogeneous.


Assuntos
Cromossomos Humanos Y/genética , Heterogeneidade Genética , Polimorfismo de Nucleotídeo Único , África do Norte , Europa (Continente) , Genética Populacional , Haplótipos , Humanos , Masculino , Repetições de Microssatélites , Oriente Médio , Filogenia , Tunísia
3.
Electrophoresis ; 33(23): 3555-63, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23160959

RESUMO

In the present study, 17 Y-chromosomal STR (Y-STR) loci were typed in 218 unrelated males from Sousse, Central-East Tunisia, to evaluate forensic and population genetic applications of the data. A total of 154 different haplotypes were identified, 127 (82.5%) of which were unique, with the most frequent haplotype occurring in 14 individuals (6.4%). The locus diversity ranged from 0.2050 at DYS392 to 0.8760 at DYS385. The haplotype diversity at the 17-loci resolution was calculated to be 0.9916, while the corresponding values for the extended (11 loci) and minimal (9 loci) haplotypes were estimated at 0.9735 and 0.9710, respectively. Comparison with 29 regional and global populations using correspondence analysis, neighbor joining (NJ) tree, and Rst genetic distance revealed that the Sousse population is highly diverse. This finding is consistent with historical data. Furthermore, the results of this study indicate a distinct genetic substructure among Tunisian populations. In conclusion, the present study demonstrated that the 17 Y-STRs analyzed are highly informative for individual identification, parentage analysis, and population genetic studies.


Assuntos
Cromossomos Humanos Y , Repetições de Microssatélites , Análise por Conglomerados , Frequência do Gene , Variação Genética , Haplótipos , Humanos , Masculino , Filogenia , Tunísia
4.
Clin Rheumatol ; 41(6): 1851-1858, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35107652

RESUMO

OBJECTIVES: Little is known about genes predisposing to systemic bone loss (SBL) in rheumatoid arthritis (RA). Therefore, we examined the association between SBL and variants of genes playing a critical role in both immune response and bone homeostasis among patients with RA. METHODS: IRAK-1 rs3027898, IRAK-2 rs3844283, IRAK-2 rs708035, IFIH1 rs1990760, CD40 rs48104850, TNFAIP3 rs2230926, and miR146-a rs2910164 were genotyped in 176 adult RA patients. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA). RESULTS: Low BMD was observed in 116 (65.9%) patients. Among them, 60 (34.1%) had low femoral neck (FN) Z score, 72 (40.9%) had low total femur (TF) Z score, and 105 (59.6%) had low lumbar spine (LS) Z score. Among all the SNPs assessed, only CD40 rs4810485 was found to be associated with reduced TF Z score with the CD40 rs4810485 T allele protecting against reduced TF Z score (OR = 0.40, 95% CI = 0.23-0.68, p = 0.0005). This association was confirmed in the multivariate logistic regression analysis (OR = 0.31, 95% CI = 0.16-0.59, p = 3.84 × 10-4). Moreover, median FN BMD was reduced among RA patients with CD40 rs4810485 GG genotype compared to RA patients harbouring CD40 rs4810485 TT and GT genotypes (0.788 ± 0.136 versus 0.826 ± 0.146 g/cm2, p = 0.001). IRAK-1 rs3027898, IRAK-2 rs3844283, rs708035, IFIH rs1990760, TNFAIP3 rs2230926, and miR146-a rs2910164 were not found to be associated with SBL. CONCLUSION: This study for the first time ever demonstrated an association between a CD40 genetic variant and SBL among patients with RA. KEY POINTS: • CD40 rs4810485 GG genotype is associated with decreased BMD among patients with RA. • CD40 rs4810485 might serve as a genetic marker for SBL in RA. • CD40 genetic variations might be integrated in future development of more effective therapeutic interventions for prevention of SBL in RA.


Assuntos
Artrite Reumatoide , Densidade Óssea , Absorciometria de Fóton , Adulto , Artrite Reumatoide/complicações , Artrite Reumatoide/genética , Densidade Óssea/genética , Antígenos CD40/genética , Colo do Fêmur , Humanos
5.
Clin Rheumatol ; 39(2): 419-424, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31650390

RESUMO

INTRODUCTION: Interleukin-1 receptor-associated kinases (IRAKs) are serine-threonine kinases involved in toll-like receptor and interleukin-1 signaling pathways. They play a key role in inflammation and innate immunity. IRAKs have been previously incriminated in autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis and inhibition of IRAKs has been recently regarded as a potential therapeutic strategy for SLE. OBJECTIVES: The aim of the present study was to test the association between IRAK2 rs708035 and rs3844283 with SLE. MATERIAL AND METHODS: IRAK2 rs708035 and rs3844283 were genotyped by mutagenically separated polymerase chain reaction (MS-PCR) in 142 SLE patients and 149 age- and gender-matched controls. RESULTS: The hyperfunctional IRAK2 rs708035 A allele was more frequent among SLE patients than controls (62.9% versus 54.7%, p = 0.046). IRAK2 rs3844283 C allele was present in 66.5% of patients and 75.5% of controls. The CC genotype was the most frequently exhibited genotype. It was carried by 45.1% of patients with SLE and 57.7% of controls. The G allele was associated with an increased risk of SLE (OR = 1.54, 95%, CI = 1.07-2.22, p = 0.017). IRAK2 rs708035 and IRAK2 rs3844283 were in linkage disequilibrium (D' = 0.64). The AG haplotype was more frequently observed in SLE patients than in controls (0.292 versus 0.194, p = 0.008). CONCLUSION: This study for the first time ever reveals the association of IRAK2 rs708035 and IRAK2 rs3844283 and the corresponding haplotypes with SLE. Our findings give additional rationale to target IRAKs in the treatment of SLE.Key Points• IRAK2 rs708035 A allele is more frequent in SLE patients than in controls and IRAK2 rs3844283 G allele is associated with SLE susceptibility.• These two alleles are in linkage disequilibrium.• The AG haplotype is associated with SLE.


Assuntos
Quinases Associadas a Receptores de Interleucina-1/genética , Lúpus Eritematoso Sistêmico/genética , Adulto , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Adulto Jovem
6.
Clin Rheumatol ; 38(4): 1067-1074, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30506403

RESUMO

OBJECTIVES: This study was aimed to investigate the association of the single nucleotide polymorphism of tumor necrosis factor receptor associated factor 6 (TRAF6), rs540386, with low bone mineral density (BMD) among patients with rheumatoid arthritis (RA). METHODS: TRAF6 rs540386 genotyping was performed by mutagenically separated PCR in a cohort of 188 (23 men, 165 women, median age, 56.2 years) adult RA patients and 224 age and gender-matched controls. BMD was measured using dual-energy X-ray absorptiometry (DXA) (Lunar Prodigy advance scans, GE Healthcare, USA). RESULTS: Among the RA patients, 64 (55 women, 9 men) had low BMD comprising of 57 patients with osteoporosis and 7 with osteopenia. Whereas TRAF6 rs540386 was not associated with RA susceptibility, it was however found to be a risk factor for reduced lumbar spine Z-score in the recessive model (OR = 3.34, 95% CI = (1.01-11.00), p = 0.038). This association was confirmed further in the multivariate logistic regression analysis taking into account several potential confounding factors (OR = 3.34 (1.01-11.00), p = 0.048). In addition, mean total femur Z-score was found to be reduced in TT patients when compared to CC + CT patients (- 1.30 ± 1.32 versus - 0.60 ± 1.05, p = 0.034). No association between TRAF6 rs540386 and local bone damage was observed. CONCLUSIONS: This study for the first time ever demonstrated an association between a genetic variant of TRAF6 and low BMD among patients with RA. Further investigations are needed to elucidate the exact role of this variant.


Assuntos
Artrite Reumatoide/genética , Densidade Óssea/genética , Fêmur/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Fator 6 Associado a Receptor de TNF/genética , Absorciometria de Fóton , Adulto , Idoso , Alelos , Artrite Reumatoide/diagnóstico por imagem , Feminino , Colo do Fêmur/diagnóstico por imagem , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco
7.
J Biomed Biotechnol ; 2008: 231904, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18475318

RESUMO

The high incidence of de novo chromosomal aberrations in a population of persons with autism suggests a causal relationship between certain chromosomal aberrations and the occurrence of isolated idiopathic autism. We report on the clinical and cytogenetic findings in a male patient with autism, no physical abnormalities and a de novo balanced (7;16)(p22.1;p16.2) translocation. G-banded chromosomes and fluorescent in situ hybridization (FISH) were used to examine the patient's karyotype as well as his parents'. FISH with specific RP11-BAC clones mapping near 7p22.1 and 16p11.2 was used to refine the location of the breakpoints. This is, in the best of our knowledge, the first report of an individual with autism and this specific chromosomal aberration.


Assuntos
Anormalidades Múltiplas , Transtorno Autístico/genética , Cromossomos Humanos Par 16/ultraestrutura , Cromossomos Humanos Par 7/ultraestrutura , Translocação Genética , Cistos Aracnóideos , Transtorno Autístico/fisiopatologia , Criança , Transtornos do Comportamento Infantil , Bandeamento Cromossômico , Transtornos Cromossômicos/genética , Transtornos Cromossômicos/patologia , Transtornos Cromossômicos/fisiopatologia , Cromossomos Artificiais Bacterianos , Cisterna Magna/patologia , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Transtornos Psicomotores
8.
Clin Rheumatol ; 37(4): 927-933, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29129009

RESUMO

This study was performed to investigate the association of the single nucleotide polymorphisms of interleukin-1 receptor-associated kinase 2 (IRAK2) rs3844283 and rs708035 with rheumatoid arthritis (RA). IRAK2 rs3844283 and rs708035genotyping was determined by mutagenically separated PCR with specifically designed primers in a cohort of 222 (30 men, 192 women, mean age 49 years) adult RA patients and 224 matched controls. IRAK2 rs3844283 C allele was detected in 66% of RA patients and 74% of controls. The CC genotype was the most frequent genotype in both RA patients (45.5%) and the controls (56.3%). The G allele was found to be associated with RA susceptibility (OR = 1.47, 95% CI = 1.10-1.96, p = 0.008). The GG genotype was found to be associated with RA in the co-dominant and the dominant models (OR = 2.03, 95% CI = 1.08-3.81, p = 0.042 and OR = 1.54, 95% CI = 1.06-2.23, p = 0.023, respectively). IRAK2 rs708035 was found not to be in the Hardy-Weinberg equilibrium. The hyperfunctional IRAK2 rs708035 A allele was more frequent in RA patients than in controls (69.9 versus 62.2%, respectively, p = 0.015). Moreover, IRAK2 rs708035 and IRAK2 rs3844283 were in linkage disequilibrium and the GA haplotype was significantly more frequent in RA patients than in controls (p = 0.034). This study for the first time ever reports the association of IRAK2 rs3844283, IRAK2 rs708035, and the corresponding haplotypes with RA. Functional studies are recommended to elucidate the risk posed by the GA haplotype for the development of RA.


Assuntos
Artrite Reumatoide/genética , Predisposição Genética para Doença , Quinases Associadas a Receptores de Interleucina-1/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
9.
J Pediatr Endocrinol Metab ; 30(12): 1245-1250, 2017 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-29176023

RESUMO

BACKGROUND: Enteroviral infections have long been suspected in having a role in ß cell destruction and therefore leading to the onset of clinical type 1 diabetes (T1D). The frequency of enterovirus (EV)-related T1D in North Africa is still unknown. The aim of the present study was to investigate the relationship between infection with EV and T1D in Tunisia. METHODS: A total of 95 T1D patients (41 children and 54 adults) and 141 healthy control subjects (57 children and 84 adults) were tested for the presence of EV-RNA by a highly sensitive nested reverse transcription-polymerase chain reaction (RT-PCR) method. RESULTS: EV-RNA was detected more frequently in plasma from diabetic patients than in plasma of controls (31.6% vs. 7.8%, p<0.0001; OR=5.45; 95% CI 2.44-12.43). RT-PCR revealed positive in 53.7% of T1D children and 14.8% of T1D adults. There was a statistically significant difference between children and adults with T1D (p<0.0001). Positivity of EV-RNA according to the time after the occurrence of the disease did not show any significant difference (p=0.34). Anti-glutamic acid decarboxylase (GAD) antibodies were not associated with EV-RNA (p=0.65). CONCLUSIONS: EV-RNA is associated with T1D mellitus in the Tunisian population especially in children. These results support the hypothesis that EV act as environmental risk factors for T1D.


Assuntos
Diabetes Mellitus Tipo 1/epidemiologia , Infecções por Enterovirus/epidemiologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/etiologia , Diabetes Mellitus Tipo 1/virologia , Enterovirus/genética , Infecções por Enterovirus/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/análise , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tunísia/epidemiologia , Adulto Jovem
10.
Genet Test Mol Biomarkers ; 21(2): 92-96, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28207326

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is characterized by the production of an array of proinflammatory cytokines through the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. Interleukin-1 receptor (IL-1R) and Toll-like receptors contain a common cytoplasmic motif the Toll/IL-1R (TIR) homology domain. This motif is required for NF-κB activation. IL-1R-associated kinase 1 (IRAK1) is a key adapter molecule recruited during the signaling cascade of the TIR. Its gene expression is regulated by the micro-RNA (miR)-146a. OBJECTIVE: We investigated the role of IRAK1 single-nucleotide polymorphism (SNP) rs3027898 (IRAK1 rs3027898) and miR-146a SNP rs2910164 (miR-146a rs2910164) in Tunisian patients with RA and their association with C reactive protein (CRP), rheumatoid factor (RF), anticyclic citrullinated peptide (anti-CCP) antibodies, and erosion. PATIENTS AND METHODS: In a cohort of 172 adult RA patients and 224 matched controls, IRAK1 rs3027898 genotyping was determined by mutagenically separated polymerase chain reaction (MS-PCR) with newly designed primers, and miR-146a rs2910164 genotyping was determined by fragment length polymorphism PCR-restriction (RFLP-PCR). RESULTS: The IRAK1 rs3027898 A allele was detected in 67% of RA patients and 70% of controls indicating that it is not associated with RA in codominant, dominant, or recessive models even after stratification by age and gender. The miR-146a rs2910164 G allele was detected in 76% of RA patients and 68% of controls, thus the C allele confers some protection based on a dominant model [CC+GC (odds ratio (95% confidence interval) = 0.6 (0.3-0.9), p = 0.03)]. No association with CRP, RF, anti-CCP, or erosion was found for either SNPs. CONCLUSION: The IRAK1 rs3027898 was not associated with RA, whereas C allele of miR-146a rs2910164 was found to be protective. Functional studies are required to investigate the exact role of miR-146a rs2910164 during RA.


Assuntos
Artrite Reumatoide/genética , Quinases Associadas a Receptores de Interleucina-1/genética , MicroRNAs/genética , Adulto , Alelos , Artrite Reumatoide/sangue , Artrite Reumatoide/enzimologia , Artrite Reumatoide/epidemiologia , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Quinases Associadas a Receptores de Interleucina-1/sangue , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fator Reumatoide/metabolismo , Tunísia/epidemiologia
11.
Am J Med Genet ; 112(4): 400-4, 2002 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-12376945

RESUMO

The TM4SF2 gene (localized at Xp11.4 between the loci DXS564 and DXS556) has been found to be mutated in one MRX family. In order to define the corresponding behavioral phenotype, global IQ and specific cognitive skills were assessed in seven males and three females of this family, independent of subject status. Mental retardation (MR) was mild in three patients and moderate in three others. Despite the broad variability of severity of MR, a cognitive profile specific to the MR in this family was documented. It was characterized by language disorder that was more marked in the articulatory component and spatial/verbal short-term memory dissociation with larger mnemonic span for spatial than for verbal cues. Linkage analysis was then performed on the basis of the cognitively determined status. Recombinations were observed with the loci DXS556 at Xp11.4 and DXS441 at Xq13.2 (maximum LOD score = 2.23 at theta = 0 for ALAS2). This localization region does not include the TM4SF2 gene that has been found mutated in both patients with MR and in one non-MR male subject of this family. The present results suggest two main hypotheses. First, TM4SF2 gene mutation could be involved in MR in this family, therefore representing accentuated intra familial phenotypic variability. Second, the structural particularity detected in the TM4SF2 gene might reflect a rare polymorphism rather than a pathogenic mutation, with the gene responsible for MR in this family being therefore more likely to be searched for in the pericentromeric region of the X chromosome.


Assuntos
Cromossomos Humanos X/genética , Deficiência Intelectual/genética , Proteínas do Tecido Nervoso/genética , Adulto , Criança , Saúde da Família , Feminino , Ligação Genética , Humanos , Deficiência Intelectual/patologia , Deficiência Intelectual/psicologia , Escore Lod , Masculino , Proteínas de Membrana , Repetições de Microssatélites , Pessoa de Meia-Idade , Mutação , Testes Neuropsicológicos , Linhagem , Tetraspaninas
12.
Am J Reprod Immunol ; 72(1): 1-4, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24689510

RESUMO

PROBLEM: We investigated the association of interleukin-10 receptor (IL10R1) loss-of-function variant A536G/S138G with recurrent pregnancy loss (RPL). METHOD OF STUDY: Study subjects comprised 300 women with ≥3 miscarriages, and 350 control women. RESULTS: Significantly higher 536G-allele frequency was seen in RPL cases, thus assigning pathogenic role for this allele. Significant difference in A536G/S138G genotypes distribution was seen between RPL cases and controls, evidenced by enrichment of 536A/G and 536G/G genotypes in RPL cases. Setting A/A genotype as reference (OR = 1.00), increased RPL risk was seen with 536A/G, and more in 536G/G carriers, thereby establishing dose-dependency. CONCLUSION: IL10R1 loss-of-function A536/S138G polymorphism may contribute to RPL pathogenesis.


Assuntos
Aborto Habitual/genética , Predisposição Genética para Doença/genética , Receptores de Interleucina-10/genética , Adulto , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Reação em Cadeia da Polimerase Multiplex , Polimorfismo de Nucleotídeo Único , Gravidez , Estudos Retrospectivos
13.
J Child Neurol ; 25(8): 1042-6, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20631224

RESUMO

Rett syndrome is a severe disorder characterized by loss of acquired skills after a period of normal development in infant girls. It is caused mainly by mutations in the MECP2 gene. In this study, we reported mutations in the MECP2 gene in 7 Tunisian patients with classic Rett syndrome. The results showed the presence of a double mutation in 1 patient: p.R306C and c.1461+98insA, which create a new hypothetical polyadenylation site in the 3(')UTR of the MECP2 gene. We also detected in another patient a new variant c.1461+92C>G in the 3(')UTR located previous to 34 bp from the polyadenylation site with a score of 4.085. This variation is located in a hypothetical splicing enhancer with a score of 1.96277 according to the ESE finder program. In the remaining 5 patients, we found 2 common mutations: p.T158M in 4 individuals and p.R168X in only 1 girl.


Assuntos
Predisposição Genética para Doença/genética , Proteína 2 de Ligação a Metil-CpG/genética , Mutação de Sentido Incorreto/genética , Síndrome de Rett/genética , Regiões 3' não Traduzidas/genética , Sequência de Bases , Criança , Biologia Computacional/métodos , Análise Mutacional de DNA/métodos , Éxons/genética , Feminino , Genótipo , Humanos , Dados de Sequência Molecular , Poliadenilação/genética , Sítios de Splice de RNA/genética , Síndrome de Rett/etnologia , Síndrome de Rett/metabolismo , Homologia de Sequência do Ácido Nucleico , Tunísia
15.
Comp Funct Genomics ; : 609684, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18509488

RESUMO

Autism is a complex neurodevelopmental disorder characterized by impairment of social interaction, language, communication, and stereotyped, repetitive behavior. Genetic predisposition to autism has been demonstrated in families and twin studies. About 5-10% of autism cases are associated with chromosomal abnormalities or monogenic disorders. The identification of genes involved in the origin of autism is expected to increase our understanding of the pathogenesis. We report on the clinical, cytogenetic, and molecular findings in a boy with autism carrying a de novo translocation t(7;16)(p22.1;p11.2). The chromosome 16 breakpoint disrupts the paralogous SLC6A8 gene also called SLC6A10 or CT2. Predicted translation of exons and RT-PCR analysis reveal specific expression of the creatine transporter paralogous in testis and brain. Several studies reported on the role of X-linked creatine transporter mutations in individuals with mental retardation, with or without autism. The existence of disruption in SLC6A8 paralogous gene associated with idiopathic autism suggests that this gene may be involved in the autistic phenotype in our patient.

19.
Hum Mol Genet ; 11(8): 981-91, 2002 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-11971879

RESUMO

Investigation of a critical region for an X-linked mental retardation (XLMR) locus led us to identify a novel Aristaless related homeobox gene (ARX ). Inherited and de novo ARX mutations, including missense mutations and in frame duplications/insertions leading to expansions of polyalanine tracts in ARX, were found in nine familial and one sporadic case of MR. In contrast to other genes involved in XLMR, ARX expression is specific to the telencephalon and ventral thalamus. Notably there is an absence of expression in the cerebellum throughout development and also in adult. The absence of detectable brain malformations in patients suggests that ARX may have an essential role, in mature neurons, required for the development of cognitive abilities.


Assuntos
Cromossomos Humanos X , Genes Homeobox , Proteínas de Homeodomínio/genética , Deficiência Intelectual/genética , Mutação , Telencéfalo/metabolismo , Fatores de Transcrição/genética , Adolescente , Adulto , Sequência de Aminoácidos , Criança , Pré-Escolar , Expressão Gênica , Proteínas de Homeodomínio/metabolismo , Humanos , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação de Sentido Incorreto , Linhagem , Peptídeos , Análise de Sequência de DNA , Análise de Sequência de Proteína , Transtornos dos Cromossomos Sexuais , Fatores de Transcrição/metabolismo
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