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1.
Allergol. immunopatol ; 47(2): 159-165, mar.-abr. 2019. tab
Artigo em Inglês | IBECS | ID: ibc-180804

RESUMO

Introduction and Objectives: Asthma is a complex genetic disorder. Several genes have been found associated with asthma. The cystic fibrosis transmembrane conductance regulator (CFTR) gene is one of them. The aim of this study was to perform a comparative analysis of the genotype and allele frequency distributions of the biallelic marker M470V within the CFTR gene on mutant and wide chromosomes. Patients and methods: The molecular approach consists in the genotyping of the M470V marker by the PCR-RFLP technique in 105 asthmatic patients, aged between four months and 17 years, and 105 healthy subjects. Results: We found a significant difference in the genotype frequencies between the two studied groups (chi2 = 9.855, P = 0.007). The V/V genotype was over represented in the asthmatic group as compared to the controls (32.38% vs. 16.19%). Whereas, the M/V genotype is more frequent in healthy subjects (40.95% vs. 28.71%). We also noted a significant difference in allelic distribution of M470V with associated diseases (chi2 = 9.610, P = 0.022). Conclusions: The present study is the first report on the distribution of the M470V polymorphism in asthmatic Tunisian patients. We noticed that the M470V variant could modulate the clinical phenotype of asthmatic patients. This preliminary study will establish the molecular basis of this disease in Tunisia


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Assuntos
Humanos , Masculino , Lactente , Pré-Escolar , Criança , Adolescente , Asma/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Genótipo , Mutação/genética , Frequência do Gene , Estudos de Associação Genética , Fenótipo
3.
Artigo em Inglês | MEDLINE | ID: mdl-30268379

RESUMO

INTRODUCTION AND OBJECTIVES: Asthma is a complex genetic disorder. Several genes have been found associated with asthma. The cystic fibrosis transmembrane conductance regulator (CFTR) gene is one of them. The aim of this study was to perform a comparative analysis of the genotype and allele frequency distributions of the biallelic marker M470V within the CFTR gene on mutant and wide chromosomes. PATIENTS AND METHODS: The molecular approach consists in the genotyping of the M470V marker by the PCR-RFLP technique in 105 asthmatic patients, aged between four months and 17 years, and 105 healthy subjects. RESULTS: We found a significant difference in the genotype frequencies between the two studied groups (χ2=9.855, P=0.007). The V/V genotype was over represented in the asthmatic group as compared to the controls (32.38% vs. 16.19%). Whereas, the M/V genotype is more frequent in healthy subjects (40.95% vs. 28.71%). We also noted a significant difference in allelic distribution of M470V with associated diseases (χ2=9.610, P=0.022). CONCLUSIONS: The present study is the first report on the distribution of the M470V polymorphism in asthmatic Tunisian patients. We noticed that the M470V variant could modulate the clinical phenotype of asthmatic patients. This preliminary study will establish the molecular basis of this disease in Tunisia.

4.
Hemoglobin ; 42(2): 96-102, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30200836

RESUMO

Sickle cell disease is a genetic disorder characterized by a hypercoagulable state. Several complications in this hemoglobinopathy are increased by thrombosis. Factor V Leiden (FVL), prothrombin (PRT) G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C mutations are major inherited risk factors of thrombotic complications. In this study, our aim was to compare the frequencies of these mutations in sickle cell patients with healthy controls. The study population comprised 35 homozygous Hb S (HBB: c.20A>T) patients, 29 compound heterozygous patients [16 Hb S/ß0-thalassemia (ß0-thal), four Hb S/ß+-thal, seven Hb S/Hb C (HBB: c.19G>A) and two Hb S/Hb O-Arab (HBB: c.364G>A)] and 100 healthy subjects. All patients and controls were subjected to laboratory investigations as well as mutation genotyping. Our findings showed a severe anemia with the lowest values of protein S (PS), protein C (PC) and antithrombin (AT) in the homozygous Hb S group compared to Hb S/Hb C and Hb S/ß-thal subjects. No significant difference in FVL genotype between patients and controls was observed, whereas high frequencies of PRT G20210A, MTHFR C677T and MTHFR A1298C mutations in the Hb S patients and a significant association between the MTHFR C677T mutation and Hb S/ß0-thal were found.

5.
Eur J Clin Pharmacol ; 74(12): 1567-1574, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30073432

RESUMO

PURPOSE: Clopidogrel non-responsiveness is multifactorial; several genetic and non-genetic factors may contribute to impaired platelet inhibition. The goal of this study is to determine the effect of the cytochrome P450 CYP2C19*2 polymorphism on the platelet response to clopidogrel in patients with and without diabetes mellitus (DM). METHODS: We conducted an observational study in patients with coronary artery disease and consequent exposure to clopidogrel therapy (75 mg/day for at least 7 consecutive days). We have analyzed two groups of patients: group I (DM patients) and group II (non-diabetes mellitus patients). Platelet reactivity was assessed by the VerifyNow P2Y12 assay and high on clopidogrel platelet reactivity (HPR) was defined as P2Y12 reaction units (PRU) ≥ 208. Genotyping for CYP2C19*2 polymorphism was performed by PCR-RFLP. RESULTS: We have included 150 subjects (76 DM and 74 non-diabetes mellitus patients). The carriage of CYP2C19*2 allele, in DM patients, was significantly associated to HPR (odds ratio (OR) 4.437, 95% confidence interval (CI) 1.134 to 17.359; p = 0.032). Furthermore, 8.4% of the variability in percent inhibition by clopidogrel could be attributed to CYP2C19*2 carrier status. However, in non-diabetes mellitus patients, there was no significant difference in platelet response to clopidogrel according to the presence or absence of CYP2C19*2 allele carriage (OR 1.260, 95% CI 0.288 to 5.522; p = 0.759). CONCLUSIONS: Our study suggests that the carriage of CYP2C19*2 polymorphism, in DM patients, might be a potential predictor of persisting HPR in these high-risk individuals. TRIAL REGISTRATION: Clinical Trials.gov NCT03373552 (Registered 13 December 2017).

6.
Afr Health Sci ; 18(3): 664-670, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30602999

RESUMO

Background: Cystic fibrosis is rare in Tunisia. Its diagnosis requires experienced specialists. Its prognosis is poor in developing countries. Objectives: To study the epidemiologic, clinical, genetic features and the therapeutic challenges of cystic fibrosis in Tunisian children. Methods: Covering a period of 21 years, this retrospective study included all patients with a definite diagnosis of cystic fibrosis from the Pediatrics Department B of The Children's Hospital of Tunis. Results: Data from 32 children (14 boys and 18 girls) were collected. The diagnosis was made during the first year of life in 28 cases. Meconium ileus was found in 5 cases, respiratory manifestations in 22 cases, chronic diarrhea in 19 cases, faltering growth in 17 cases and a pseudo Barter syndrome in 2 cases. The sweat chloride test was positive in all cases. The most frequent mutation was F508del (56% of cases). Respiratory complications marked the outcome. Among our 32 patients, 15 patients (50%) died at an average age of 5 years and 3 months, mainly due to respiratory failure. The mean age of the surviving patients was 5 years. Conclusion: Cystic fibrosis prognosis is poor in our series compared to developed countries due to the longer diagnostic delay and the limited therapeutic options.


Assuntos
Fibrose Cística/epidemiologia , Pré-Escolar , Fibrose Cística/genética , Fibrose Cística/patologia , Fibrose Cística/terapia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Tunísia/epidemiologia
7.
Ann Biol Clin (Paris) ; 75(4): 466-473, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28751295

RESUMO

Pseudo-Bartter syndrome (PBS) describes an uncommon complication of cystic fibrosis leading to hypochloraemic, hypokalaemic metabolic alkalosis. PBS as the sole manifestation of cystic fibrosis in children is extremely rare and has never been described in patients carrying 5T variant. We report a clinical, biochemical and genetic study of a four year-old boy presenting a pseudo-Bartter syndrome as the sole manifestation of cystic fibrosis. All 27 exons and the flanking intron regions of the CFTR gene were analysed by PCR and direct sequencing. Direct sequencing was also used to analyse TGmTn and M470V polymorphisms in the patient and his parents. Two sweat tests were abnormal with elevated chloride levels at 78 and 88 mmol/L. DNA sequencing revealed a heterozygous mutation 711+1 G>T and an IVS8-T5 allele. The mutation 711+1 G>T is in trans with the IVS8-T5-TG11 allele and the child carried M470/V470 genotype. To the best of our knowledge, the genotype 711+1 G>T /IVS8-5T found in our patient is described for the first time. The role of TG11-5T-V470 allele in cases of cystic fibrosis with PB syndrome remains to be determined.


Assuntos
Síndrome de Bartter/diagnóstico , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/diagnóstico , Fibrose Cística/genética , Mutação , Síndrome de Bartter/genética , Pré-Escolar , Fibrose Cística/complicações , Diagnóstico Diferencial , Humanos , Masculino , Polimorfismo Genético
8.
Electrophoresis ; 38(17): 2210-2218, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28543614

RESUMO

HbA1c is used for monitoring diabetic balance. In this paper we report an assessment of the analytical performances of Capillarys 2 Flex Piercing (C2FP) for HbA1c measurement using CE (Capillary Electrophoresis). CLSI (Clinical and Laboratory Standard Institute) protocols are used for the evaluation of apparatus performances: precision, linearity, method comparison, trueness and common interferences. HbA1c CVs average in intra-assay was 1.6% between run imprecision CV ranged from 0.1 to 1.8%. The linearity was demonstrated between 4.7 and 15.0%. The comparison study revealed that Bland Altman plot mean difference was equal to -0.03 (CI 95% (-0.05 to -0.0003)) and Passing-Bablok regression intercept was -0.05, CI95%(-0.13 -  -0.05); slope: 1.00, CI95%[1.00-1.01]. A strong correlation (r > 0.99) was proved. No significant effects of hemoglobin variants were seen with CE on HbA1c measurement. No problem related to sample-to-sample carry over was noted. No interferences of LA1c and cHb were observed. CE allowed quantification of HbA1c even at low level of total hemoglobin (40 g/L) in contrast to HPLC. Furthermore, this analyzer offered the opportunity of quantifying the HbA2 simultaneously with HbA1c . This evaluation showed that C2FP is a convenient system for the control of diabetes and the detection of hemoglobinopathies.


Assuntos
Eletroforese Capilar/métodos , Eletroforese Capilar/normas , Hemoglobina A Glicada/análise , Diabetes Mellitus/sangue , Diabetes Mellitus/metabolismo , Humanos , Modelos Lineares , Reprodutibilidade dos Testes , Tunísia
9.
J Sports Med Phys Fitness ; 57(9): 1217-1226, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27441913

RESUMO

BACKGROUND: Achieving excellence in track and field athletes requires specific mental skills. The aim of the present study was to compare the mental skills between elite sprint and endurance athletes. METHODS: Forty elite athletes (age 20.55±2.22 years, body mass 74.8±7.9 kg, height 1.70±0.1 m) participated in the present study. The athletes were classified into two groups according to their genetic polymorphism to physical activity: Endurance group (allele I, N.=20) and power group (allele D, N.=20). The mental skills were assessed by means of Ottawa Mental Skill Assessment Tool-3 inventory (OMSAT-3: based in foundation mental skills, psychosomatic skills, and cognitive skills subscales) before the competition period. Furthermore, genetic data were also collected. Sprint and endurance runners were participating in Tunisian National championship. RESULTS: The results showed a significant difference between elite sprint and endurance runners in the foundation mental and psychosomatic skills subscales (all, P<0.05). Typically, the present study revealed that goal setting, commitment, stress reactions, fear control, imagery, competition planning and mental practice were significantly higher among the elite sprint runners compared to the endurance runners (all, P<0.05). Findings from this study could confirm the widely acclaimed research assumption that mental skills, such as goal setting, commitment and mental practice, are the predictor variables of power performances, while endurance performances are associated with different mental skills components. CONCLUSIONS: Finally, the results may inform applied practitioners regarding the differences in mental skill demands between power and endurance athletes and the genetic predisposition of practitioners.


Assuntos
Polimorfismo Genético , Corrida/psicologia , Atletismo/psicologia , Adolescente , Adulto , Humanos , Masculino , Resistência Física/fisiologia , Projetos Piloto , Adulto Jovem
10.
Hemoglobin ; 40(6): 411-416, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27829304

RESUMO

The C/EBPE gene, located in 14q11.2, encodes for a B/zip-type transcription factor. The C/EBPɛ is involved in terminal differentiation and functional maturity of granulocyte progenitor cells and in cell apoptosis during myeloid differentiation. A C/EBPE gene has recently been described as a candidate gene involved in clinical variability of ß-thalassemia (ß-thal). In this study, the C/EBPE gene was sequenced in 146 subjects divided into the severe type of ß-thal major (ß-TM) and moderate type of ß-thal intermedia (ß-TI), and a control group. The analysis identified the rs45496295 (C > T) polymorphism in the heterozygous state in 73.9% ß-TI patients, which was not the case in the ß-TM patients or in the control group. Thus, the T allele is consequently associated with the ß-TI group (p = 10-3). According to the Human Splicing Finder (version 3.0, Marseille, France), the presence of the rs45496295 polymorphism leads the creation of a new intronic exotic splicing enhancer (ESE) site. Moreover, the T allele of rs45496295 is associated with a lower transfusion regimen (p = 10-3) and a higher pretransfusion hemoglobin (Hb) rate (p = .006). The comparison of several factors concerning T allele carriers and non-carriers showed that the T allele does not act on the Hb F rate. The T allele of rs45496295, associated with moderate type of ß-thal, seems to modify the C/EBPɛ action, thereby preventing the hemolysis.


Assuntos
Proteínas Estimuladoras de Ligação a CCAAT/genética , Polimorfismo de Nucleotídeo Único , Talassemia beta/genética , Adulto , Hemoglobina Fetal/metabolismo , Hemoglobinas/metabolismo , Hemólise/genética , Humanos
11.
Clin Chim Acta ; 460: 55-62, 2016 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-27343352

RESUMO

BACKGROUND: Congenital disorders of fibrinogen are rare diseases resulting in the complete absence (afibrinogenemia), reduced concentration (hypofibrinogenemia) or altered function of circulating fibrinogen (dysfibrinogenemia). A combination of two different fibrinogen abnormalities with a significant functional and secretion defect (hypodysfibrinogenemia) reported in Tunisian family members, was investigated in this study. METHODS: The coagulation-related tests, kinetics of fibrin polymerization and lysis and fibrinogen analysis using gel electrophoresis were performed in the family members to characterize fibrinogen abnormalities. All exons including exon-intron boundaries of fibrinogen genes were screened by direct sequencing. RESULTS: Mutational screening of the fibrinogen genes disclosed novel missense mutations, BßCys197Arg, in exon 4 of the fibrinogen Bß-chain gene. After the loose of its partner in Bß-chain, the γCys135 was probably disulfide-bridged to its corresponding Cys residue of another abnormal fibrinogen molecule, forming dimmer with an abnormal electrophoretic profile. Homozygous form carried by the proband found to be directly involved in the bleeding phenotype by affecting fibrin polymerization. In contrast, affected family members bearing the heterozygous mutation showed an impaired fibrin polymerization and fibrinolysis leading to thrombosis. CONCLUSION: These results suggest that this mutation could alter the extremely conserved conformations of fibrinogen D domain and D-D lateral regions on fibrin assembly.


Assuntos
Afibrinogenemia/genética , Fibrinogênios Anormais/genética , Mutação de Sentido Incorreto , Análise Mutacional de DNA , Saúde da Família , Feminino , Fibrinogênio/genética , Genótipo , Hemorragia/genética , Humanos , Pessoa de Meia-Idade , Linhagem , Trombose/genética , Tunísia
12.
Ann Biol Clin (Paris) ; 74(2): 219-26, 2016 Mar-Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27029726

RESUMO

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy. More than 200 mutations in the G6PD gene have been described. In Tunisia, the A-African and the B-Mediterranean mutations predominate the mutational spectrum. The purpose of this study was to apply the amplification refractory mutation system (ARMS-PCR) to the identification of Gd A+, Gd A- and Gd B- variants in a cohort of deficient individuals and to establish a phenotype/genotype association. 90 subjects were screened for enzymatic deficiency by spectrophotometric assay. The molecular analyses were performed in a group of 50 unrelated patients. Of the 54 altered chromosomes examined, 60% had the Gd A- mutation, 18% showed the Gd B- mutation and in 20% of cases, no mutations have been identified. The ARMS-PCR showed complete concordance with the endonuclease cleavage reference method and agreed perfectly with previous Tunisian studies where Gd A- and Gd B- were the most encountered. Also, similarities in spectrum mutations with North African and Mediterranean countries suggest gene migration from Africa to Europe through Spain. In conclusion, ARMS has been introduced in this study for common G6PD alleles identification in Tunisia. It gives some advantages compared to the traditional endonuclease digestion method since it is more convenient and timesaving and also offers the possibility to be applied in mass screening surveys.


Assuntos
Análise Mutacional de DNA/métodos , Estudos de Associação Genética/métodos , Deficiência de Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/genética , Mutação de Sentido Incorreto , Reação em Cadeia da Polimerase/métodos , Adolescente , Adulto , Substituição de Aminoácidos , Criança , Pré-Escolar , Feminino , Frequência do Gene , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Tunísia , Adulto Jovem
13.
J Clin Lab Anal ; 30(5): 392-8, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27086580

RESUMO

BACKGROUNDS: ß-Thalassemia is one of the most prevalent worldwide autosomal recessive disorders. It presents a great molecular heterogeneity resulting from more than 200 causative mutations in the ß-globin gene. In Tunisia, ß-thalassemia represents the most prevalent monogenic hemoglobin disorder with 2.21% of carriers. Efficient and reliable mutation-screening methods are essential in order to establish appropriate prevention programs for at risk couples. The aim of the present study is to develop an efficient method based on the denaturing high-performance liquid chromatography (DHPLC) in which the whole ß-globin gene (HBB) is screened for mutations covering about 90% of the spectrum. METHODS: We have performed the validation of a DHPLC assay for direct genotyping of 11 known ß-thalassemia mutations in the Tunisian population. RESULTS: DHPLC assay was established based on the analysis of 62 archival ß-thalassemia samples previously genotyped then validated with full concordance on 50 tests with blind randomized samples previously genotyped with DNA sequencing and with 96% of consistency on 40 samples as a prospective study. CONCLUSION: Compared to other genotyping techniques, the DHPLC method can meet the requirements of direct genotyping of known ß-thalassemia mutations in Tunisia and to be applied as a powerful tool for the genetic screening of prenatal and postnatal individuals.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Testes Genéticos/métodos , Mutação/genética , Globinas beta/genética , Talassemia beta/diagnóstico , Análise Mutacional de DNA , Feminino , Genótipo , Humanos , Masculino , Tunísia/epidemiologia , Talassemia beta/genética
15.
J Child Neurol ; 31(7): 843-9, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26759449

RESUMO

Autism has been reported in untreated patients with phenylketonuria. The authors aimed to explore autism in 15 Tunisian and 4 Algerian phenylketonuria patients, and report their clinical, biochemical and molecular peculiarities. The Childhood Autism Rating Scale and the Autism Diagnostic Interview-Revised were used for the diagnosis of autism. Five exons of phenylalanine hydroxylase gene (7, 6, 10, 11, and 5) were amplified by polymerase chain reaction and directly sequenced. Among these patients, 15 were suffering from autism at the time of evaluation. Six mutations were identified: p.E280K, p.G352Vfs, IVS10nt11, p.I224T, p.R261Q, and p.R252W. There was no correlation between autism and mutations affecting the phenylalanine hydroxylase gene, but the age of diet onset was the determining factor in autistic symptoms' evolution.


Assuntos
Transtorno Autístico/complicações , Transtorno Autístico/genética , Fenilalanina Hidroxilase/genética , Fenilcetonúrias/complicações , Fenilcetonúrias/genética , Adolescente , Fatores Etários , Argélia , Transtorno Autístico/metabolismo , Criança , Pré-Escolar , Éxons , Família , Feminino , Frequência do Gene , Humanos , Masculino , Mutação , Fenilcetonúrias/dietoterapia , Fenilcetonúrias/metabolismo , Prognóstico , Escalas de Graduação Psiquiátrica , Tunísia
16.
J Neural Transm (Vienna) ; 123(3): 317-21, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26456241

RESUMO

Angiotensin-converting enzyme (ACE) has shown altered activity in patients with neurological diseases. An insertion/deletion (I/D) polymorphism of the ACE gene encoding angiotensin-converting enzyme has been reported to be associated with the risk for Alzheimer's disease (AD), and is generally considered to be a disorder primarily affecting memory. We conducted a case-control study in a sample composed of 85 sporadic AD patients and 90 age- and sex-matched controls to investigate the possible effect of the polymorphism and cognitive profile. Our data revealed an association between the ACE polymorphism and AD risk. There was a significant difference in the ACE allele or genotype frequencies between cases and controls. The D/D genotype showed an increased risk for AD and in the amnestic group and the effect was independent on ApoE genotypes.


Assuntos
Doença de Alzheimer/genética , Apolipoproteína E4/genética , Predisposição Genética para Doença/genética , Peptidil Dipeptidase A/genética , Idoso , Alelos , Estudos de Casos e Controles , Cognição , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tunísia
17.
Int J Mycobacteriol ; 5 Suppl 1: S151, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28043520

RESUMO

OBJECTIVE/BACKGROUND: Tuberculosis is a major public health problem and the emergence of drug resistance complicates the situation even more. It is therefore crucial to implement all conclusions from the studies that aim at a better understanding of the molecular mechanisms which govern the emergence and the evolution of drug resistance. The aim of this study is to assess the degree of involvement of the inhA and katG genes in the acquisition of isoniazid resistance in clinical strains of Mycobacterium tuberculosis. METHODS: The inhA and katG genes were sequenced in 21 strains of M. tuberculosis with different resistance profiles and from different regions. RESULTS: Analysis of the sequences obtained by comparison to those of the reference strain H37Rv showed that 95.2% had mutations. KatG S315T was the most common mutation (85.7%). The mutation katG T275A was revealed in two strains (9.5%). Two different point mutations in the inhA gene and its promoter region were identified as C-15T and G56A at a frequency equal to 14% and 10%, respectively. The G56A mutation is a new silent mutation. Our study showed no correlation between found mutations and multidrug resistance. Among the 21 strains studied, only one strain showed no mutations. CONCLUSION: In terms of this study, we characterized the mutations involved in resistance to isoniazid. katG S315T was by far the most frequent mutation, followed by C-15T. The frequency of these mutations was concordant with those reported in literature including those in intermediate tuberculosis endemic countries.

18.
Clin Lab ; 62(11): 2139-2143, 2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28164663

RESUMO

BACKGROUND: In this work, we are interested to study for the first time the extragenic polymorphic marker MP6d9 in cystic fibrosis and healthy cohort in Tunisia to establish the contribution of MP6d9 polymorphism in the phenotypic variability of CF patients. METHODS: Our study enrolled 112 CF patients and 100 healthy controls. The analysis of the polymorphic marker MP6d9 was performed using the PCR-RFLP technique. RESULTS: Statistical difference was found in the genotype and allelic distribution between CF patients and control groups. We found that the 2/2 genotype was higher in CF patients than in controls (58.9% vs 23%). We noted that the 2/2 genotype is associated with severe clinical manifestations. CONCLUSION: Based on the above data, it seems that this genotype has led to the deterioration of our patient's clinical manifestation. This study enabled us to understanding the involvement of the MP6d9 marker in the CF clinical expression in the Tunisian population.


Assuntos
Fibrose Cística/genética , Marcadores Genéticos , Polimorfismo Genético , Adolescente , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Estudos de Casos e Controles , Criança , Pré-Escolar , Fibrose Cística/diagnóstico , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Lactente , Recém-Nascido , Masculino , Fenótipo , Projetos Piloto , Polimorfismo de Fragmento de Restrição , Índice de Gravidade de Doença , Tunísia
19.
J Neural Transm (Vienna) ; 123(4): 451-3, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26695639

RESUMO

Several clinical phenotypes were associated with presenilin 1 (PSEN1) mutation in early-onset familial Alzheimer's disease (EOFAD). We report the clinical phenotype of two members of a familial dementia kindred who presented with EOFAD and early psychiatric syndrome as behavioral abnormalities. Sequence analysis of the index patient and his brother's PSEN1 transcript revealed a novel T > C transition in exon 4 which was determined as a missense substitution at position 248 of the coding sequence (cDNA. 248T > C).


Assuntos
Doença de Alzheimer/genética , Mutação , Presenilina-1/genética , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Linhagem , Fenótipo
20.
Neurobiol Aging ; 36(10): 2904.e9-11, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26145164

RESUMO

A minority of Alzheimer disease (AD) patients begin presenting symptoms before the age of 65 years. A familial aggregation is often found in this group of early-onset AD, and, in a subset of families, the pattern of inheritance is consistent with autosomal dominant inheritance. Fully penetrant variants in amyloid precursor protein, presenilin 1 (PSEN1), and presenilin 2 are the only causative mutations reported for autosomal dominant AD. This study is to explore the PSEN1 gene mutation in a Tunisian familial Alzheimer's disease. The patient in this family showed a novel missense mutation in exon 4 of the PSEN1 gene (complementary DNA 248T>C), altering isoleucine to threonine at 83 position. Because the change occurred in conserved domains of this gene, and cosegregated with affected family member, we suggested that this change may have a mutagenic and probably pathogenic effect.


Assuntos
Doença de Alzheimer/genética , Estudos de Associação Genética , Mutação de Sentido Incorreto , Presenilina-1/genética , Idoso , Éxons/genética , Feminino , Genes Dominantes/genética , Humanos , Isoleucina/genética , Masculino , Pessoa de Meia-Idade , Estrutura Terciária de Proteína/genética , Treonina/genética , Tunísia
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