Assuntos
Displasia Ectodérmica Anidrótica Tipo 1/genética , Ectodisplasinas/genética , Receptor Edar/genética , Mutação , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , México , Linhagem , Fenótipo , Adulto JovemRESUMO
INTRODUCTION: Parkinson's disease (PD) is a common neurodegenerative disease which begins in adulthood. Its incidence in Mexico is estimated to be 40-50 cases per 100,000 inhabitants/year and is the fourth reason for medical care in the National Institute of Neurology and Neurosurgery. The protein alpha-synuclein, SNCA, plays a key role in the pathology of PD, and its polymorphisms have been associated with an increased risk of developing the disease. AIM: To evaluate the risk of PD represented by the polymorphisms rs2619364, rs2619363, rs2736990, rs7684318, rs17016074, rs356219, rs356220 and rs356203 of SNCA in a sample of Mexican subjects. SUBJECTS AND METHODS: Altogether 171 patients diagnosed with PD and 171 gender- and age-paired controls were assessed by means of real-time polymerase chain reaction, and a statistical analysis was performed to determine the association between the polymorphisms and the disease. RESULTS: The SNCA variants rs356220, rs356203, rs7684318 and rs2736990 were associated with the disease and form two haplotypes with a high risk of developing sporadic PD in the Mexican population. CONCLUSIONS: Variations in SNCA are a risk factor for the development of PD and can act as specific genetic biomarkers as a diagnostic support tool in sporadic PD for Mexican mestizo patients.
TITLE: Frecuencia de polimorfismos de nucleotido unico y haplotipos de alfa-sinucleina asociados con la enfermedad de Parkinson esporadica en poblacion mexicana.Introduccion. La enfermedad de Parkinson (EP) es una entidad neurodegenerativa comun de inicio en la etapa adulta. Su incidencia en Mexico se estima en 40-50 casos por 100.000 habitantes/año y constituye la cuarta causa de atencion medica en el Instituto Nacional de Neurologia y Neurocirugia. La proteina alfa-sinucleina, SNCA, es clave en la patologia de la EP y sus polimorfismos se han asociado a un riesgo aumentado de desarrollarla. Objetivo. Evaluar el riesgo que representan los polimorfismos rs2619364, rs2619363, rs2736990, rs7684318, rs17016074, rs356219, rs356220 y rs356203 de SNCA en una muestra de sujetos mexicanos para la EP. Sujetos y metodos. Se evaluaron 171 pacientes con diagnostico de EP y 171 controles pareados por sexo y edad mediante reaccion en cadena de la polimerasa en tiempo real, y se realizo un analisis estadistico para determinar la asociacion de los polimorfismos con la enfermedad. Resultados. Las variantes rs356220, rs356203, rs7684318 y rs2736990 de SNCA estan asociadas a la enfermedad y forman dos haplotipos de riesgo elevado para desarrollar EP esporadica en la poblacion mexicana. Conclusiones. Las variaciones en SNCA son un factor de riesgo para desarrollar EP y pueden ser biomarcadores geneticos especificos para pacientes mestizos mexicanos como herramienta de apoyo diagnostico en la EP esporadica.
Assuntos
Predisposição Genética para Doença , Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único , alfa-Sinucleína/genética , Genótipo , Haplótipos , Humanos , MéxicoRESUMO
We aimed to explore the possible influence of CYP2C9 (*2, *3 and IVS8-109 A>T), CYP2C19 (*2, *3 and *17) and ABCB1 (1236C>T, 2677G>A/T and 3435C>T) on phenytoin (PHT) plasma concentrations in 64 Mexican Mestizo (MM) patients with epilepsy currently treated with PHT in mono- (n=25) and polytherapy (n=39). Genotype and allele frequencies of these variants were also estimated in 300 MM healthy volunteers. Linear regression models were used to assess associations between the dependent variables (PHT plasma concentration and dose-corrected PHT concentration) with independent variables (CYP2C9, CYP2C19 and ABCB1 genotypes, ABCB1 haplotypes, age, sex, weight, and polytherapy). In multivariate models, CYP2C9 IVS8-109 T was significantly associated with higher PHT plasma concentrations (t(64)=2.27; P=0.03). Moreover, this allele was more frequent in the supratherapeutic group as compared with the subtherapeutic group (0.13 versus 0.03, respectively; P=0.05, Fisher's exact test). Results suggest that CYP2C9 IVS8-109 T allele may decrease CYP2C9 enzymatic activity on PHT. More research is needed to confirm findings.
Assuntos
Anticonvulsivantes/sangue , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C9/genética , Epilepsia/tratamento farmacológico , Epilepsia/genética , Variantes Farmacogenômicos/genética , Fenitoína/sangue , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Adolescente , Adulto , Idoso , Anticonvulsivantes/administração & dosagem , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Citocromo P-450 CYP2C19/metabolismo , Citocromo P-450 CYP2C9/metabolismo , Monitoramento de Medicamentos , Epilepsia/sangue , Epilepsia/etnologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Modelos Lineares , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Análise Multivariada , Fenótipo , Fenitoína/administração & dosagem , Fatores de Risco , Resultado do Tratamento , Adulto JovemAssuntos
Glucosilceramidase/genética , Mutação , Doença de Parkinson/genética , Idade de Início , Idoso , Códon , Feminino , Humanos , Masculino , México , Pessoa de Meia-IdadeRESUMO
Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal disorder exhibiting a wide clinical spectrum ranging from minimal anomalies to classic CCD. Mutations scattered throughout the entire CBFA1 gene have been related to this disorder. However, it seems that most of them affect the highly conserved Runt domain, abolishing the DNA-binding ability of this transcription factor. Moreover, no systematic effect has been found to relate the type of mutation to the severity of the clinical features. In this paper, we studied two unrelated patients with classic CCD. DNA analysis revealed two novel mutations and three undescribed polymorphisms. One of the substitutions was a missense mutation in the Q/A domain leading to the replacement of a polar residue by a nonpolar one (158 A --> T [Q53L]). The second was an uncommon heterozygous stop codon mutation (1565 G --> C [X522S]) which theoretically results in a longer protein with 23 additional amino acids. This is the first report of this type of mutation in CBFA1. We discuss the possible consequences of these mutant sequences, although no phenotype-genotype correlation could be established. Our findings expand the existing number of allelic variants in this pathology.
Assuntos
Displasia Cleidocraniana/genética , Mutação , Proteínas de Neoplasias , Fatores de Transcrição/genética , Adolescente , Pré-Escolar , Subunidade alfa 1 de Fator de Ligação ao Core , Análise Mutacional de DNA , Feminino , Humanos , Masculino , México , Dados de Sequência Molecular , Polimorfismo GenéticoRESUMO
We report a Turner patient aged 22 years with a 45,X/46,X,del(X)(q23) karyotype. Late replication studies showed preferential inactivation of the deleted X chromosome; FISH studies with a probe for total human telomeres showed hybridisation signal in the telomeres on both the normal and the deleted X chromosomes. Microsatellite analysis in the proposita and her family permitted us to conclude to the maternal origin of the deleted X chromosome, and to detect using the marker DXS1106 (Xq22) a probable meiotic recombination event above the breakage point suggesting that the deletion occurred underneath this point. The mild Turner stigmata may be explained by the 45,X cell line, and the gonadal dysgenesis probably by a partial deletion of the gonadal dysgenesis region Xq13-q23 (excluding Xq22).