<i>PKD2</i> gene mutation analysis in Korean autosomal dominant polycystic kidney disease patients using two‐dimensional gene scanning

Chung, Wookyung; Kim, H.; Hwang, Young Hwan; Kim, S. Y.; Ko, Ah-Ra; Ro, Han; Lee, K. B.; Oh, Kook Hwan; Ahn, Curie

doi:10.1111/j.1399-0004.2006.00721.x

Cited by 10 publications

(4 citation statements)

References 27 publications

(30 reference statements)

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“…It is classified as definitely pathogenic according to the ADPKD Mutation Database ( http://pkdb.mayo.edu/cgi ). This mutation was also described in 1 Korean [19] and 1 French family [9] previously. We also identified 1 synonymous variant in exon 1, c.420G>A, p.G140G, along with 2 intronic and 1 3′UTR (untranslated region) variants ( Table 3 ).…”

Section: Resultssupporting

confidence: 66%

PKD2 mutation in an Iranian autosomal dominant polycystic kidney disease family with misleading linkage analysis data

Entezam

Khatami

Saddadi

et al. 2016

Kidney Research and Clinical Practice

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BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is the most common genetic renal disorder caused by mutation in 2 genes PKD1 and PKD2. Thus far, no mutation is identified in approximately 10% of ADPKD families, which can suggest further locus heterogeneity. Owing to the complexity of direct mutation detection, linkage analysis can initially identify the responsible gene in appropriate affected families. Here, we evaluated an Iranian ADPKD family apparently unlinked to both PKD1 and PKD2 genes. This is one of the pioneer studies in genetic analysis of ADPKD in Iranian population.MethodsLinkage reanalysis was performed by regenotyping of flanking microsatellite markers in 8 individuals of the ADPKD family. Direct mutation analysis was performed by Sanger sequencing.ResultsMutation analysis revealed a pathogenic mutation (c.1094+1G>A) in the PKD2 gene in the proband. Analyzing 2 healthy and 4 clinically affected members confirmed the correct segregation of the mutation within the family and also ruled out the disease in 1 suspected individual. Misinterpretation of the linkage data was due to the occurrence of 1 crossing over between the PKD2 intragenic and the nearest downstream marker (D4S2929). Homozygosity of upstream markers caused the recombination indistinguishable.ConclusionAlthough analysis of additive informative polymorphic markers can overcome the misleading haplotype data, it is limited because of the lack of other highly polymorphic microsatellite markers closer to the gene. Direct mutation screening can identify the causative mutation in the apparently unlinked pedigree; moreover, it is the only approach to achieve the confirmed diagnosis in individuals with equivocal imaging results.

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Section: Resultssupporting

confidence: 66%

PKD2 mutation in an Iranian autosomal dominant polycystic kidney disease family with misleading linkage analysis data

Entezam

Khatami

Saddadi

et al. 2016

Kidney Research and Clinical Practice

View full text Add to dashboard Cite

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“…This approach had a mutation detection rate ranging from 6.6% (6/91 unrelated individuals) [ 18 ] to 13.7% (7/51 families) [ 20 ]. Other methods previously used include two-dimensional gene scanning followed by DGGE and direct sequencing of PKD2 ; a mutation detection rate of 13.0% (6/46 patients) was reported using this approach [ 28 ]. Linkage analysis using PCR and polyacrylamide gel electrophoresis for PKD1 and PKD2 resulted in a mutation detection rate of 81.3% (39/48 families) [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of novel PKD1 and PKD2 mutations in Korean patients with autosomal dominant polycystic kidney disease

et al. 2014

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BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder. It is caused by mutations in the PKD1 and PKD2 genes, and manifests as progressive cyst growth and renal enlargement, resulting in renal failure. Although there have been a few studies on the frequency and spectrum of mutations in PKD1 and PKD2 in Korean patients with ADPKD, only exons 36–46, excluding the duplicated region, were analyzed, which makes it difficult to determine accurate mutation frequencies and mutation spectra.MethodsWe performed sequence analysis of 20 consecutive unrelated ADPKD patients using long-range polymerase chain reaction (PCR) to avoid pseudogene amplification, followed by exon-specific PCR and sequencing of the all exons of these two genes. Multiplex ligation-dependent probe amplification was performed in patients in whom pathogenic mutations in PKD1 or PKD2 were not identified by LR-PCR and direct sequencing to detect large genomic rearrangements.ResultsAll patients met the diagnostic criteria of ADPKD, and pathogenic mutations were found in 18 patients (90.0%), comprising 15 mutations in PKD1 and three in PKD2. Among 10 novel mutations, eight mutations were found in the PKD1 gene while two mutations were found in the PKD2 gene. Eight of 14 PKD1 mutations (57.1%) were located in the duplicated region.ConclusionsThis study expands the spectra of mutations in the PKD1 and PKD2 genes and shows that the mutation frequencies of these genes in Korean ADPKD patients are similar to those reported in other ethnicities. Sequence analysis, including analysis of the duplicated region, is essential for molecular diagnosis of ADPKD.

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“…Nevertheless, a recurrent mutation PKD2 p.R803X was found in three families in Taiwan and five families in other populations. 30,[36][37][38][39] This frequent mutation could be related to its location in the CpG dinucleotide site that is susceptible to mutations, or it could be a founder mutation that derived from the common ancestor. 35 The frequency of large rearrangements reported in a large ADPKD cohort (n ¼ 202) was 4%.…”

Section: Discussionmentioning

confidence: 99%

Novel PKD1 and PKD2 mutations in Taiwanese patients with autosomal dominant polycystic kidney disease

et al. 2013

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Autosomal dominant polycystic kidney disease (ADPKD) is a heterogeneous disease caused by mutations in PKD1 and PKD2. The genotype-phenotype correlations are not completely understood. We performed direct PCR-sequencing plus multiplex ligation-dependent probe amplification for PKD1 and PKD2 in 46 unrelated patients. Disease-causing mutations were identified in 30 (65%) patients: 23 (77%) patients have mutations in PKD1 and 7 (23%) have mutations in PKD2. Nonsense, splicing or frame-shifting mutations were found in 18 patients, exon duplication in 1 and missense mutations in 11 patients. Two likely PKD1 hypomorphic alleles (p.Arg2477His and p.Arg3439Trp) segregated with mild disease in a family. A total of 34 mutations were identified and 17 (50%) of which are novel. The median age at onset of dialysis was significantly earlier in patients with PKD1 mutations (52 years) than in patients with PKD2 mutations (65.5 years) and those with an undetermined genotype (67 years) by survival analysis (log-rank test, P=0.014). Patients carrying PKD1-truncating mutations have a trend toward earlier initiation of dialysis compared with carriers of non-truncating mutations (52 years vs 57 years, P=0.061). A family history of dialysis before 55 years was more common in PKD1 patients than in others (P<0.05). In conclusion, this study identified novel mutations in PKD1 and PKD2 and demonstrated the presence of PKD1 hypomorphic alleles in Taiwanese patients. Patients carrying PKD1 mutations, especially those with truncating mutations, could have a more rapidly progressive disease than others. These results might have implications for diagnosis and risk stratification in patients with ADPKD.

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PKD2 gene mutation analysis in Korean autosomal dominant polycystic kidney disease patients using two‐dimensional gene scanning

Cited by 10 publications

References 27 publications

PKD2 mutation in an Iranian autosomal dominant polycystic kidney disease family with misleading linkage analysis data

PKD2 mutation in an Iranian autosomal dominant polycystic kidney disease family with misleading linkage analysis data

Identification of novel PKD1 and PKD2 mutations in Korean patients with autosomal dominant polycystic kidney disease

Novel PKD1 and PKD2 mutations in Taiwanese patients with autosomal dominant polycystic kidney disease

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