Genotypes of autosomal dominant polycystic kidney disease in Japanese

Mizoguchi, Michiko; Tamura, Takashi; Yamaki, Akiko; Higashihara, Eiji; Shimizu, Yoshiko

doi:10.1007/s10038-002-8654-5

Cited by 15 publications

(7 citation statements)

References 22 publications

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“…The percentage of non-autosomal dominant PKD patients is also less than 10% among different populations (3,4). Several studies from around the world report similar results as mentioned above; for example Mizoguchi et al in 21 Japanese ADPKD families, including 96 individuals and 57 affected members, reported that 17 families (81%) had linkage to PKD1, 2 families (10%); PKD2 and 2 families did not have linkage to either PKD1 or PKD2 (14). Another study was performed by colleagues on 48 Korean families that the results were composed of PKD1 (79%) and PKD2 (21%) (15).…”

Section: Discussionsupporting

confidence: 65%

“…The calculation of LOD scores for this two-point linkage analysis was done via the FASTLINK software. The resultant data in each family were integrated by means of Bayesian weighting formula for the likelihood estimation of a family to one or other locus (14). The genotyping of individuals includes descendent and married-in patients, where extracted and the founders of genotypes were reconstructed.…”

Section: Linkage Analysis and Haplotype Constructionmentioning

confidence: 99%

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Linkage Analysis of Autosomal Dominant Polycystic Kidney Disease in Iranian Families through PKD1 and PKD2 DNA Microsatellite Markers

et al. 2017

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Background: Autosomal dominant polycystic kidney disease (ADPKD) is a heterogeneous disorder. Two known loci, including PKD1 (16p13.3) and PKD2 (4q21), as well as a third locus that is not clearly identified, cause ADPKD. Objectives: The aim of this study was to assess the genetic linkage of 4 linked microsatellite markers of PKD genes (PKD1 and PKD2) to ADPKD for genetic screening of familiar PKD patients in Yazd. Methods: This familial case-control study was conducted among 18 families. The linkage analysis was performed using 2 pairs of polymorphic microsatellite markers that are closely linked to the PKD1 gene (16AC2.5 and KG8) and 2 other pairs closely linked to the PKD2 gene (D4S231 and D4S423). These markers were detected through PCR of tandem repeats method and polyacrylamide gel electrophoresis. Results: The disease was linked to PKD1 about 77.8%, PKD2 16.7% of the families, and to neither gene in 5.5%, according to LOD scores and allele segregation analysis. It also found relatively high heterozygosity and polymorphism information contents (PIC) values for 3 markers including 16AC2.5 (PIC: 0.798) for PKD1 gene and D4S423 (PIC: 0.807) as well as D4S231 (PIC: 0.741) for PKD2 gene. However, it seems that KG8 marker has no significant linkage to the PKD1 gene (PIC: 0.329) among Yazd PKD patients. Conclusions: These results show similarity to another report from Iranian families and according to these similar results, it seems that 16AC2.5 and D4S423 markers would provide an improved framework for genetic screening of ADPKD patients among familiar PKD patients in Yazd.

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Section: Discussionsupporting

confidence: 65%

Section: Linkage Analysis and Haplotype Constructionmentioning

confidence: 99%

Linkage Analysis of Autosomal Dominant Polycystic Kidney Disease in Iranian Families through PKD1 and PKD2 DNA Microsatellite Markers

et al. 2017

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“…Furthermore, these two markers are known as suitable markers for ADPKD genetic testing in most studied populations. [ 8 13 14 15 ] In addition, for the first time, we found D16S475 to be highly informative in our population. This marker has also been reported as a suitable marker in some other studies.…”

Section: Discussionsupporting

confidence: 58%

“…Among the microsatellite markers reported in the PKD1 gene region, two extragenic markers, i.e., D16S475 and D16S291, and one intragenic marker, i.e., D16S3252 have been shown to have a high degree of heterozygosity (HET). [ 13 14 15 16 ] However, investigation of these markers has been rarely performed in the Iranian population. In this study, the HET and polymorphism information content (PIC) values for the PKD1 markers D16S475, D16S291, and D16S3252 were determined in a normal population of Iran.…”

Section: Introductionmentioning

confidence: 99%

Heterozygosity analysis of polycystic kidney disease 1 gene microsatellite markers for linkage analysis of autosomal dominant polycystic kidney disease type 1 in the iranian population

et al. 2017

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Background:Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of end-stage renal disease. Although imaging techniques are a means of accurate diagnosis when the cysts appear in the third or fourth decades of the patient's life, they are of little value for early diagnosis. Genetic tests are required for preimplantation genetic diagnosis, decision-making for kidney donation to an affected relative. Although mutation of the polycystic kidney disease (PKD1) gene is solely responsible for the most cases of ADPKD, direct genetic testing is limited by the large size of this gene and the presence of many mutations without hot spots. Therefore, indirect diagnosis with linkage analysis using informative microsatellite markers has been suggested.Materials and Methods:In this study, we assessed the informativeness of the PKD1 gene markers D16S475, D16S291, and D16S3252 in Iranian population. Using specific primers, fluorescent polymerase chain reaction (PCR) was performed on genomic DNA extracted from fifty unrelated individuals. PCR products were analyzed by the ALFexpress DNA sequencer system, and the number and frequency of alleles were determined to calculate the heterozygosity (HET) and polymorphism information content (PIC) values.Results:We found that the HET and PIC values for the D16S475 marker are 0.92 and 0.91, respectively. These two values are 0.82 and 0.80 for D16S291 and 0.50 and 0.47 for D16S3252, respectively.Conclusion:Based on this data, D16S475 and D16S291 are highly and D16S3252 is moderately informative for indirect genetic diagnosis of PKD1 mutations in this population.

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“…There is an argument about the existence of PKD3, however, no more genes have been identified. 6,7 The severity of renal disease in ADPKD is highly variable ranging from neonatal death, through typical presentations with end-stage renal disease (ESRD) in the sixth decade to adequate function into old age. 8 The phenotypic variability is due to heterogeneity at the genic and allelic levels as accepted.…”

Section: Introductionmentioning

confidence: 99%

Two novel mutations affecting the same splice site ofPKD1correlate with different phenotypes in ADPKD

Yuan

et al. 2014

Renal Failure

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Genetic heterogeneity is the main factor for significant variation in the course of autosomal dominant polycystic kidney disease (ADPKD). PKD1 patients have more severe renal outcomes compared with PKD2 patients. Co-inheritance of a mutation in both genes is associated with more severe phenotypes than that found with either mutation alone. However, the genotype-phenotype relationship is far from clear in ADPKD. Here, we observed two novel mutations, PKD1:c.12444G4A and PKD1:c.12444 + 1G4A, which alter the same splice donor site of intron 45, correlate with different renal outcomes. To explain the phenomenon, we analyzed the genic and allelic background of the patients, as well as the genetic modifiers, DKK3 and HNF-1b as suggested. Only PKD1 variants were found, which highlights the allelic influence of PKD1 gene to be the last candidate factor. Segregation analysis, online mutation prediction, and recurrence mutation searching were applied to sort the variants. However, none of variants was found to be damaging or associated with the disease except PKD1:c.12444G4A and PKD1:c.12444 + 1G4A. Cloning and sequencing of the mutated cDNA sequences had shown unexpected different splicing effects caused by the mutations. PKD1:c.12444 + 1G4A definitely destroyed the native splice site and created a novel donor site with truncating effect on PC1. In contrast, PKD1:c.12444G4A mainly weakened the site and decreased the expression of normal PC1. Since PC1 negatively regulates cell proliferation in the process of cyst formation and enlargement, our observation may explain this new genotype-phenotype correlation and help to improve genetic counseling and diagnosis of the disease.

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Genotypes of autosomal dominant polycystic kidney disease in Japanese

Cited by 15 publications

References 22 publications

Linkage Analysis of Autosomal Dominant Polycystic Kidney Disease in Iranian Families through PKD1 and PKD2 DNA Microsatellite Markers

Linkage Analysis of Autosomal Dominant Polycystic Kidney Disease in Iranian Families through PKD1 and PKD2 DNA Microsatellite Markers

Heterozygosity analysis of polycystic kidney disease 1 gene microsatellite markers for linkage analysis of autosomal dominant polycystic kidney disease type 1 in the iranian population

Two novel mutations affecting the same splice site ofPKD1correlate with different phenotypes in ADPKD

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