RESUMEN
Cerebrotendinous xanthomatosis (CTX) is a lipid storage disease caused by a deficiency of the mitochondrial enzyme 27-sterol hydroxylase (CYP 27), due to mutations in its gene. In this study we report on mutations in 58 patients with CTX out of 32 unrelated families. Eight of these were novel mutations, two of which were found together with two already known pathogenic mutations. Twelve mutations found in this patient group have been described in the literature. In the patients from 31 families, mutations were found in both alleles. In the literature, 28 mutations in 67 patients with CTX out of 44 families have been described. Pooling our patient group and the patients from the literature together, 37 different mutations in 125 patients out of 74 families were obtained. Identical mutations have been found in families from different ethnic backgrounds. In 41% of all the patients, CYP 27 gene mutations are found in the region of exons 6-8. This region encodes for adrenodoxin and haem binding sites of the protein. Of these 125 patients, a genotype-phenotype analysis was done for 79 homozygous patients harbouring 23 different mutations, out of 45 families. The patients with compound heterozygous mutations were left out of the genotype-phenotype analysis. The genotype-phenotype analysis did not reveal any correlation.
Asunto(s)
Sistema Enzimático del Citocromo P-450/genética , Mutación , Esteroide Hidroxilasas/genética , Xantomatosis Cerebrotendinosa/genética , Xantomatosis Cerebrotendinosa/patología , Adolescente , Adulto , Edad de Inicio , Sustitución de Aminoácidos , Encéfalo/patología , Niño , China , Colestanotriol 26-Monooxigenasa , Etnicidad/genética , Europa (Continente) , Exones , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Países Bajos , Mutación Puntual , Eliminación de Secuencia , Túnez , Xantomatosis Cerebrotendinosa/fisiopatologíaRESUMEN
The fragile X syndrome is associated with an expanding CGG repeat in the 5' untranslated region of the first exon of the FMR1 gene. Subsequent methylation of the promoter region inhibits expression of the FMR1 gene. In two clinically normal brothers large, expanded CGG repeats and cytogenetically visible fragile sites were found. The FMR1 promoter was unmethylated and both RNA and protein could be detected. This indicates that inactivation of the FMR1 gene and not repeat expansion itself results in the fragile X phenotype. We conclude that repeat expansion does not necessarily induce methylation and that methylation is no absolute requirement for the induction of fragile sites.
Asunto(s)
Síndrome del Cromosoma X Frágil/genética , Mutación , Proteínas del Tejido Nervioso/genética , Proteínas de Unión al ARN , Adolescente , Adulto , Anciano , Mapeo Cromosómico , Femenino , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil , Expresión Génica , Humanos , Masculino , Linaje , Fenotipo , Repeticiones de Trinucleótidos/genéticaRESUMEN
The X region of the protein A gene of Staphylococcus aureus contains a highly polymorphic sequence which is composed of repeats of 24 bp. We used amplification by PCR to investigate whether this region could be used to discriminate between epidemic and nonepidemic methicillin-resistant S. aureus (MRSA) strains. Most epidemic MRSA strains (24 of 33) harbored more than seven repeats, while most nonepidemic MRSA strains (10 of 14) contained seven or fewer repeats. It is conceivable that a longer X region results in a better exposition of the Fc-binding region of protein A, thereby facilitating colonization of host surfaces and contributing to the epidemic phenotype.