RESUMO
UNLABELLED: Haemophilia A (HA) is X-chromosome linked bleeding disorders caused by deficiency of the coagulation factor VIII (FVIII). It is caused by FVIII gene intron 22 inversion (Inv22) in approximately 45% and by intron 1 inversion (Inv1) in 5% of the patients. Both inversions occur as a result of intrachromosomal recombination between homologous regions, in intron 1 or 22 and their extragenic copy located telomeric to the FVIII gene. The aim of this study was to analyze the presence of these mutations in 25 HA Costa Rican families. PATIENTS, METHODS: We studied 34 HA patients and 110 unrelated obligate members and possible carriers for the presence of Inv22or Inv1. Standard analyses of the factor VIII gene were used incl. Southern blot and long-range polymerase chain reaction for inversion analysis. RESULTS: We found altered Inv22 restriction profiles in 21 patients and 37 carriers. It was found type 1 and type 2 of the inversion of Inv22. During the screening for Inv1 among the HA patient, who were Inv22 negative, we did not found this mutation. DISCUSSION: Our data highlight the importance of the analysis of Inv22 for their association with development of inhibitors in the HA patients and we are continuous searching of Inv1 mutation. This knowledge represents a step for genetic counseling and prevention of the inhibitor development.
Assuntos
Fator VIII/genética , Hemofilia A/genética , Cromossomos Humanos X/genética , Costa Rica , DNA/sangue , DNA/genética , DNA/isolamento & purificação , Feminino , Hemofilia A/sangue , Humanos , Íntrons/genética , Masculino , Linhagem , Reação em Cadeia da Polimerase/métodos , Mapeamento por Restrição , Índice de Gravidade de DoençaRESUMO
Inherited factor X deficiency (FXD) is a rare (1:1,000,000) recessive bleeding disorder. The clinical and laboratory phenotypes of FXD are poorly correlated and few regional studies on the genotype and the clinical manifestations of FXD are known. To understand the association between clinical manifestations and causative genotype, detailed evaluation of bleeding pattern in a high number of patients is needed. This international study analysed the phenotype and genotype of 102 subjects from Central Europe (Germany, Poland and Slovakia) and Latin America (Costa Rica and Venezuela) with causative mutations in the F10 gene, via sequencing. Twenty-eight homozygous, seven compound-heterozygous and 67 heterozygous FXD subjects were characterized. Twenty-nine different causative mutations, including 15 novel mutations, were analysed. Spontaneous bleeding symptoms in 42 symptomatic individuals (26 homozygous, seven compound heterozygous and nine heterozygous) comprised easy bruising (55%), haematoma (43%), epistaxis (36%), haemarthrosis (33%), intracranial haemorrhage (ICH; 21%), and gastrointestinal (GI) haemorrhage (12%). The manifestation of bleeding symptoms in 9 of 67 (13%) symptomatic heterozygous subjects is described. The bleeding patterns of the enrolled patients showed differences that are associated with the types of F10 mutation, and the corresponding genotypes. The homozygous patients were evaluated for genotype-phenotype correlation. The results suggested that ICH seems to be associated with the F10 mutation Gly380Arg, and possibly with the mutations IVS7-1G>A and Tyr163delAT. A tentative association of other mutations to severe symptoms such as haemarthrosis and GI haemorrhage is reported. The severity of FXD, the genotype-phenotype association, and the results of regional studies are discussed.
Assuntos
Deficiência do Fator X/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Costa Rica/epidemiologia , Epistaxe/epidemiologia , Epistaxe/genética , Europa (Continente)/epidemiologia , Fator X/genética , Deficiência do Fator X/congênito , Deficiência do Fator X/epidemiologia , Feminino , Hemartrose/epidemiologia , Hemartrose/genética , Hematoma/epidemiologia , Hematoma/genética , Hemorragia/epidemiologia , Hemorragia/genética , Heterozigoto , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Fenótipo , Prevalência , Venezuela/epidemiologiaRESUMO
The purpose of this study was to determine the blood levels of selected nutritional status indicators and the dietary intake of Costa Rican Cabécar Indians aged 10 to 16 years. The results showed that 65% of the adolescents had an adequate body mass index (BMI) for their age, and 32% had a BMI < 5th percentile. Likewise, the study revealed a high prevalence of anemia (57%), deficient serum folate levels (54%), deficient vitamin B12 levels (31%), and subclinical vitamin A deficiency (10%). Additionally, the youngsters had elevated prevalences of high triglyceride levels (77%), borderline high-density lipoprotein (HDL) cholesterol levels (46%), homocysteine levels > 10 micromol/L (29%), and homozygous mutation of methylenetetrahydrofolate reductase (MTHFR) (49%). The diet was poor, being high in saturated fat and low in polyunsaturated fat, fiber, and several micronutrients. The dietary intakes of more than 55% of the adolescents did not meet 50% of the estimated average requirements (EAR) for zinc, vitamin A, vitamin C, vitamin B12, vitamin B2, and folate. Furthermore, a high prevalence of parasitosis was found (68%). Our results show an adolescent Cabécar population with a mosaic of nutritional deficiencies and cardiovascular risk factors.
Assuntos
Fenômenos Fisiológicos da Nutrição do Adolescente , Transtornos da Nutrição Infantil/epidemiologia , Fenômenos Fisiológicos da Nutrição Infantil , Dieta , Gorduras na Dieta/administração & dosagem , Estado Nutricional , Adolescente , Biomarcadores/sangue , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Criança , Transtornos da Nutrição Infantil/etiologia , Transtornos da Nutrição Infantil/prevenção & controle , Costa Rica/epidemiologia , Costa Rica/etnologia , Inquéritos sobre Dietas , Ingestão de Energia , Feminino , Humanos , Lipoproteínas/sangue , Masculino , Necessidades Nutricionais , Doenças Parasitárias/complicações , Doenças Parasitárias/epidemiologia , Fatores de Risco , Triglicerídeos/sangueRESUMO
Hemophilia A and B are X-chromosome linked bleeding disorders caused by deficiency of the respective coagulation factor VIII and IX. Affected individuals develop a variable phenotype of hemorrhage caused by a broad range of mutations within the Factor VIII or Factor IX gene. Here, were report the results of the molecular diagnosis in a five Costa Rican families affected with Hemophilia. Methods of indirect and direct molecular diagnosis are applied in three Hemophilia A and two Hemophilia B families from Costa Rica as well as preconditions, practicability and facilities of this diagnosis. In two families with Hemophilia A and both families with Hemophilia B the causative mutation could be detected by Southern blotting, polymerase chain reaction or sequence analysis. One Hemophilia A family could only analyzed by linkage analysis using genomic markers.
Assuntos
Humanos , Masculino , Feminino , Fator IX/genética , Fator VIII/genética , Hemofilia A/diagnóstico , Hemofilia B/diagnóstico , Mutação/genética , Costa Rica , Hemofilia A/genética , Hemofilia B/genética , Linhagem , Marcadores Genéticos , Reação em Cadeia da Polimerase , Southern BlottingRESUMO
Hemophilia A and B are X-chromosome linked bleeding disorders caused by deficiency of the respective coagulation factor VIII and IX. Affected individuals develop a variable phenotype of hemorrhage caused by a broad range of mutations within the Factor VIII or Factor IX gene. Here, were report the results of the molecular diagnosis in a five Costa Rican families affected with Hemophilia. Methods of indirect and direct molecular diagnosis are applied in three Hemophilia A and two Hemophilia B families from Costa Rica as well as preconditions, practicability and facilities of this diagnosis. In two families with Hemophilia A and both families with Hemophilia B the causative mutation could be detected by Southern blotting, polymerase chain reaction or sequence analysis. One Hemophilia A family could only analyzed by linkage analysis using genomic markers.
Assuntos
Fator IX/genética , Fator VIII/genética , Hemofilia A/diagnóstico , Hemofilia B/diagnóstico , Mutação/genética , Southern Blotting , Costa Rica , Feminino , Marcadores Genéticos , Hemofilia A/genética , Hemofilia B/genética , Humanos , Masculino , Linhagem , Reação em Cadeia da PolimeraseRESUMO
Introducción: El estudio se orientó a buscar trombofilias en pacientes jóvenes con infarto de miocardio tanto genéticas, como las de las proteínas anticoagulantes. Material y métodos: Las pruebas de laboratorio que se usaron para la medición del fibrinógeno fue el método de Clauss, para la proteína C y Antitrombina III (AIII) se utilizó un método cromogénico, para la S un método coagulométrico y las pruebas genéticas por Reacción de Cadena Polimerasa (PCR). Se seleccionaron 51 pacientes jóvenes menores de 45 años con infarto agudo del miocardio y 43 pacientes sanos de grupo control de las mismas edades. Resultados: Se encontró un 85 por ciento de pacientes masculinos y 15 por ciento femeninos. Las variables que fueron factores de riesgo estadísticamente significativas fueron el sexo P = 0.0023 demostrando que por cada 4.19 hombres sufren infarto existe una mujer. El índice de masa corporal fue significativamente mayor en los pacientes infartados con un valor de P = 0.002733 y existió asociación estadísticamente significativa con obstrucciones coronarias. La hipertensión también fue estadísticamente significativa valor de P = 0.00167. Para el nivel de colesterol total la medida en los pacientes sanos fue de 166mg/dl contra 213mg/dl en los pacientes con infarto con un valor de P = 0.000527mg/dl. Para el HDL colsesterol el 78 por ciento de los pacientes infartados tenían niveles iguales o menores de 35mg/dl y existió asociación estadísticamente significativa con la presencia de obstrucciones coronarias. El nivel de triglicéridos mostró una asociación estadísticamente significativa con un valor de P= 0.000161mg/dl. El 58 por ciento de los pacientes infartados tenína un nivel elevado de LDL colesterol. En el anális de las proteínas anticoagulantes la población enferma tuvo niveles significativamente menores que el grupo control tanto para la proteína S y la C. En el análisis de cruces hay una asociación estadísticamente significativa entre la frecuencia alélica de la mutación de la enzima metiltetrahidrofolato reductasa y tener niveles menores de las proteínas C y S tanto en los pacientes enfermos como en los sanos que son homocigotas a la mutación. No hubo asociación estadísticamente significativa para el factor V Leyden y la variable 20210 de Protombina. Conclusión: En los pacientes menores de 45 con infarto del miocardio existen claros marcadores de riesgo para enfermedad coronaria al compararlos con sujetos sanos de una edad similar.
Assuntos
Pessoa de Meia-Idade , Genética , Infarto do Miocárdio , Trombose , Costa RicaAssuntos
Homocisteína/sangue , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Complexo Vitamínico B/sangue , Análise de Variância , Ácido Fólico/sangue , Genótipo , Humanos , Indígenas Sul-Americanos/genética , Metilenotetra-Hidrofolato Redutase (NADPH2) , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/sangue , Polimorfismo Genético , Venezuela/etnologia , Vitamina B 12/sangueRESUMO
Resistance to activated protein C (APC) is the most common inherited risk factor for venous thrombosis. Most cases of APC resistance are caused by the point mutation nt 1691 G-A in factor V gene, referred to as factor V Leiden mutation. As initially shown in a Dutch population, this mutation has a carrier rate of 2.9%, the most frequent genetic disposition for thrombophilia and deep venous thrombosis. By large-scale epidemiological studies we have determined the prevalence of factor V Leiden mutation in populations from Poland (200), Argentina (215), Venezuela (126), Costa Rica (196), and India (150). The prevalences have been estimated for Poland (Warsaw) 5.0%, Argentina (Buenos Aires) 5.1%, Venezuela (Valencia) 1.6%, Costa Rica (San José) 2.0%, and India (Punjab) 1.3%. Based on worldwide distribution, it can be hypothesized that the factor V Leiden mutation has originated and accumulated in central European Caucasians and spread over the world by migration.