Genetic heterogencity of PKD1 and PKD2 genes in Iran and determination of the genotype/phenotype correlations is several families with autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease [ADPKD] is the most common genetic nephropathy, which is characterized by replacement of renal parenchyma with multiple cysts. In Iran, the disease prevalence within the chronic hemodialysis patient population is approximately 8-10%. So far, three genetic loci have been identified to be responsible for ADPKD. Little information is available concerning the pattern of linkage in Iranian population. In the present study, the linkage analysis was performed using three pairs of polymorphic microsatellite markers including 16AC2.5-CA [D16S291], SM7-CA [D16S283] and KG8-CA [intragenic marker at the 3' end of the gene]. These markers are closely linked to the ADPKD1 locus and three pairs of the selected polymorphic microsatellite markers including YUNCA9 [D4S231], AFM155xe11 [D4S1534] and AFM224x6 [D4S423], which were closely linked to the ADPKD2 locus. In parallel, the genomic DNA of 150 unrelated healthy individuals was used to determine frequency, heterozygosity rate and polymorphic information content [PIC] for each marker. In our study, haplotypes were constructed in a number of ADPKD families using respective markers. Assignment of the disease gene loci was performed following phasing and haplotype construction, genotype/phenotype correlations were deduced from the constructed haplotypes. Analysis of clinical data confirms a milder ADPKD phenotype for PKD2 families in Iran. Our results showed relatively high heterozygosity rates and PIC values for some markers, while the most informative markers were KG8 [PIC: 0.772] and 16AC2.5 [PIC: 0.689] for PKD1 gene and AFM224x6 [PIC: 0.712] for PKD2 gene. We report here the first molecular genetic study of ADPKD and the existence of locus heterogeneity for ADPKD in Iranian population by performing linkage analysis on 15 affected families. Eleven families showed linkage to PKD1 and two families linked to PKD2 gene. In 2 families, PKD1 markers were common in all affected members but PKD2 markers were not informative

Molecular study of pkd[1]and pkd[2] genes by linkage analysis and determining the genotype/phenotype correlations in several Iranian families with autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease [ADPKD] is an inherited disorder with genetic heterogeneity. Up to three loci are involved in this disease, PKD1 on chromosome 16p 13.3, PKD2 on 4q21, and a third locus of unknown location.Here we report the first molecular genetic study of ADPKD and the existence of locus heterogeneity for ADPKD in the Iranian population by performing linkage analysis on 15 affected families.Eleven families showed linkage to PKD1 and two families showed linkage to PKD2. In two families, PKD1 markers are common in all affected members but PKD2 markers were not informative.The results of this study demonstrate significant locus heterogeneity in autosomal dominant PKD in Iran. Analysis of clinical data confirms a milder ADPKD phenotype for PKD2 families. Our results showed relatively high heterozygosity rates and PIC values for some markers, while the most informative markers were KG8 and 16AC2.5 for PKD1 gene and AFM224x6 for PKD2 gene