RESUMEN
Linkage analysis was performed on 22 Bulgarian families with polycystic kidney disease (PKD) ascertained through the hemodialysis centers of two medical schools. A total of 128 affected and 59 unaffected individuals, and 54 spouses have been investigated using eight polymorphic markers linked to PKD1 and nine markers to PKD2. The results demonstrate locus heterogeneity with 0.67 as the maximum likelihood value of alpha, i.e., the proportion of families linked to PKD1. In five families, the results suggest linkage to PKD2 and observed recombinants place the gene between loci D4S1544 and D4S1542. In one family, two double recombinants for closely linked markers on chromosome 16 and on chromosome 4 give evidence for the lack of linkage to either PKD1 or PKD2, thus suggesting the involvement of a third locus. Analysis of clinical data in the PKD1 group versus the unlinked group shows no significant differences in the severity of the disease.
Asunto(s)
Heterogeneidad Genética , Riñón Poliquístico Autosómico Dominante/epidemiología , Riñón Poliquístico Autosómico Dominante/genética , Adulto , Bulgaria/epidemiología , Recolección de Datos , Femenino , Marcadores Genéticos , Humanos , Escala de Lod , Masculino , Persona de Mediana Edad , Fenotipo , Riñón Poliquístico Autosómico Dominante/etiología , Polimorfismo de Longitud del Fragmento de Restricción , Proteínas/genética , Recombinación Genética , Canales Catiónicos TRPPRESUMEN
Indirect DNA analysis was performed on 12 families totalling 80 people. The analysis used five genetic markers flanking the gene: 3'HVR, pGGG, 218 EP6, 24-1, 26-6. In 11 of the families (92%), a linkage with the PKD1 gene in chromosome 16 was established. In one family, the disease did not segregate with the polymorphic markers of PKD1-locus, thus excluding any possibility that a mutation in this locus was the cause of the autosomal dominant polycystic kidney disease (ADPKD). A correlation was discovered between the positive echographic diagnosis and the genotype in the PKD1-dependent patients with ADPKD. In 28.6 percent of the children studied, and in 12.5 percent of subjects under the age of 30, the echographic diagnosis was corrected through DNA analysis.
