DNA Testing for Live Kidney Donors at Risk for Autosomal Dominant Polycystic Kidney Disease

Huang, Edmund; Samaniego-Picota, Millie; McCune, Thomas R.; Melancon, J. Keith; Montgomery, Robert A.; Ugarte, Richard; Kraus, Edward S.; Womer, Karl L.; Rabb, Hamid; Watnick, Terry

doi:10.1097/tp.0b013e318191e729

Cited by 45 publications

(25 citation statements)

References 18 publications

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“…In 2009 an algorithm was proposed to determine when molecular testing may be useful for evaluating potential kidney donors in families affected by ADPKD. 47 However, these criteria did not differentiate between analyses made by ultrasonography and those made by the more sensitive CT and MRI methods, which could result in ~50% of potential donors requiring genetic testing at a considerable cost. 40,48 In our opinion, this algorithm also seems too conservative; for instance, it recommends that all potential donors from a family affected by ADPKD who are less than 40 years of age and are found to have three cysts or fewer by ultrasonography, CT, or MRI, should undergo genetic testing.…”

Section: Diagnosing Adpkd: Molecular Testingmentioning

confidence: 99%

Molecular diagnostics for autosomal dominant polycystic kidney disease

2010

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Autosomal dominant polycystic kidney disease (ADPKD) is a common nephropathy caused by mutations in either PKD1 or PKD2. Mutations in PKD1 account for ~85% of cases and cause more severe disease than mutations in PKD2. Diagnosis of ADPKD before the onset of symptoms is usually performed using renal imaging by either ultrasonography, CT or MRI. In general, these modalities are reliable for the diagnosis of ADPKD in older individuals. However, molecular testing can be valuable when a definite diagnosis is required in young individuals, in individuals with a negative family history of ADPKD, and to facilitate preimplantation genetic diagnosis. Although linkage-based diagnostic approaches are feasible in large families, direct mutation screening is generally more applicable. As ADPKD displays a high level of allelic heterogeneity, complete screening of both genes is required. Consequently, such screening approaches are expensive. Screening of individuals with ADPKD detects mutations in up to 91% of cases. However, only ~65% of patients have definite mutations with ~26% having nondefinite changes that require further evaluation. Collation of known variants in the ADPKD mutation database and systematic scoring of nondefinite variants is increasing the diagnostic value of molecular screening. Genic information can be of prognostic value and recent investigation of hypomorphic PKD1 alleles suggests that allelic information may also be valuable in some atypical cases. In the future, when effective therapies are developed for ADPKD, molecular testing may become increasingly widespread. Rapid developments in DNA sequencing may also revolutionize testing.

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Section: Diagnosing Adpkd: Molecular Testingmentioning

confidence: 99%

Molecular diagnostics for autosomal dominant polycystic kidney disease

2010

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“…Genetic testing, however, can facilitate the diagnosis in patients whose renal phenotypes are unclear and in patients for whom there is lack information regarding family history; it may also help identify donors for renal transplantation [9]. However, modern genetic testing methods are currently not part of the standard of care.…”

Section: Introductionmentioning

confidence: 99%

Technical Evaluation: Identification of Pathogenic Mutations in PKD1 and PKD2 in Patients with Autosomal Dominant Polycystic Kidney Disease by Next-Generation Sequencing and Use of a Comprehensive New Classification System

et al. 2016

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Genetic testing of PKD1 and PKD2 is expected to play an increasingly important role in determining allelic influences in autosomal dominant polycystic kidney disease (ADPKD) in the near future. However, to date, genetic testing is not commonly employed because it is expensive, complicated because of genetic heterogeneity, and does not easily identify pathogenic variants. In this study, we developed a genetic testing system based on next-generation sequencing (NGS), long-range polymerase chain reaction, and a new software package. The new software package integrated seven databases and provided access to five cloud-based computing systems. The database integrated 241 polymorphic nonpathogenic variants detected in 140 healthy Japanese volunteers aged >35 years, who were confirmed by ultrasonography as having no cysts in either kidney. Using this system, we identified 60 novel and 30 known pathogenic mutations in 101 Japanese patients with ADPKD, with an overall detection rate of 89.1% (90/101) [95% confidence interval (CI), 83.0%–95.2%]. The sensitivity of the system increased to 93.1% (94/101) (95% CI, 88.1%–98.0%) when combined with multiplex ligation-dependent probe amplification analysis, making it sufficient for use in a clinical setting. In 82 (87.2%) of the patients, pathogenic mutations were detected in PKD1 (95% CI, 79.0%–92.5%), whereas in 12 (12.8%) patients pathogenic mutations were detected in PKD2 (95% CI, 7.5%–21.0%); this is consistent with previously reported findings. In addition, we were able to reconfirm our pathogenic mutation identification results using Sanger sequencing. In conclusion, we developed a high-sensitivity NGS-based system and successfully employed it to identify pathogenic mutations in PKD1 and PKD2 in Japanese patients with ADPKD.

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“…Huang et al [39] [35]. It is considered safe to proceed with kidney donation if imaging studies and genetic studies exclude ADPKD.…”

Section: Apkdmentioning

confidence: 99%