RESUMEN
A missense G209A mutation of the alpha-synuclein gene was recently described in a large Contursi kindred with Parkinson's disease (PD). The objective of this study is to determine if the mutation G209A of the alpha-synuclein gene was present in 10 Brazilian families with PD. PD patients were recruited from movement disorders clinics of Brazil. A family history with two or more affected in relatives was the inclusion criterion for this study. The alpha-synuclein G209A mutation assay was made using polymerase chain reaction and the restriction enzyme Tsp45I. Ten patients from 10 unrelated families were studied. The mean age of PD onset was 42.7 years old. We did not find the G209A mutation in our 10 families with PD. Our results suggest that alpha-synuclein mutation G209A is uncommon in Brazilian PD families.
Asunto(s)
Mutación/genética , Proteínas del Tejido Nervioso/genética , Enfermedad de Parkinson/genética , Adulto , Edad de Inicio , Anciano , Brasil , Femenino , Humanos , Masculino , Persona de Mediana Edad , Linaje , Reacción en Cadena de la Polimerasa , Mapeo Restrictivo , Sinucleínas , alfa-SinucleínaRESUMEN
Ellis-van Creveld syndrome (EvC, MIM 225500) is an autosomal recessive skeletal dysplasia characterized by short limbs, short ribs, postaxial polydactyly and dysplastic nails and teeth. Congenital cardiac defects, most commonly a defect of primary atrial septation producing a common atrium, occur in 60% of affected individuals. The disease was mapped to chromosome 4p16 in nine Amish subpedigrees and single pedigrees from Mexico, Ecuador and Brazil. Weyers acrodental dysostosis (MIM 193530), an autosomal dominant disorder with a similar but milder phenotype, has been mapped in a single pedigree to an area including the EvC critical region. We have identified a new gene (EVC), encoding a 992-amino-acid protein, that is mutated in individuals with EvC. We identified a splice-donor change in an Amish pedigree and six truncating mutations and a single amino acid deletion in seven pedigrees. The heterozygous carriers of these mutations did not manifest features of EvC. We found two heterozygous missense mutations associated with a phenotype, one in a man with Weyers acrodental dysostosis and another in a father and his daughter, who both have the heart defect characteristic of EvC and polydactyly, but not short stature. We suggest that EvC and Weyers acrodental dysostosis are allelic conditions.
Asunto(s)
Cromosomas Humanos Par 4/genética , Disostosis/genética , Síndrome de Ellis-Van Creveld/genética , Etnicidad/genética , Genes , Proteínas de la Membrana/genética , Anomalías Dentarias/genética , Empalme Alternativo , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Secuencia de Bases , Brasil/epidemiología , Mapeo Cromosómico , Enanismo/genética , Síndrome de Ellis-Van Creveld/etnología , Etiquetas de Secuencia Expresada , Femenino , Dedos/anomalías , Genes Dominantes , Cardiopatías Congénitas/genética , Heterocigoto , Humanos , Incisivo/anomalías , Leucina Zippers/genética , Masculino , Proteínas de la Membrana/fisiología , Repeticiones de Microsatélite , Datos de Secuencia Molecular , Linaje , Pennsylvania/epidemiología , Fenotipo , Mutación Puntual , Polimorfismo Conformacional Retorcido-Simple , Proteínas , Recombinación Genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , SíndromeRESUMEN
Ellis-van Creveld syndrome (EVC) is an autosomal recessive disorder characterized by disproportionate dwarfism, polydactyly, and congenital heart disease. This rare disorder is found with increased frequency among the Old Order Amish community in Lancaster County, Pennsylvania. We have used linkage analysis to localize the gene responsible for the EVC phenotype in nine interrelated Amish pedigrees and three unrelated families from Mexico, Ecuador, and Brazil. We now report the linkage for the Ellis-van Creveld syndrome gene to markers on the distal short arm of human chromosome 4, with Zmax = 6.91 at theta = 0.02 for marker HOX7, in a region proximal to the FGFR3 gene responsible for the achondroplasia phenotype.