scholarly journals POS-423 MAINSTREAMING GENETIC TESTING FOR ADULT NEPHROLOGY: A MODEL FOR A PUBLICLY FUNDED HEALTHCARE SYSTEM FOR AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE AND FOCAL SEGMENTAL GLOMERULOSCLEROSIS

2021 ◽  
Vol 6 (4) ◽  
pp. S182-S183
Author(s):  
M. ELLIOTT ◽  
L. Colvin James ◽  
E. Simms ◽  
P. Sharma ◽  
M. Elliott ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Healthcare System ◽  
Focal Segmental Glomerulosclerosis ◽  
Autosomal Dominant ◽  
Publicly Funded ◽  
Polycystic Kidney ◽  
Segmental Glomerulosclerosis ◽  
Autosomal Dominant Polycystic Kidney

scholarly journals Mainstreaming Genetic Testing for Adult Patients With Autosomal Dominant Polycystic Kidney Disease

2021 ◽  
Vol 8 ◽  
pp. 205435812110550
Author(s):  
Mark D. Elliott ◽  
Leslie C. James ◽  
Emily L. Simms ◽  
Priyana Sharma ◽  
Louis P. Girard ◽  
...  
Keyword(s):  
Health Care ◽  
Genetic Testing ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Retrospective Cohort ◽  
Autosomal Dominant ◽  
Return Of Results ◽  
Publicly Funded ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney

Purpose: Genetic testing results are currently obtained approximately 1 year after referral to a medical genetics team for autosomal dominant polycystic kidney disease (ADPKD). We evaluated a mainstream genetic testing (MGT) pathway whereby the nephrology team provided pre-test counseling and selection of patients with suspected ADPKD for genetic testing prior to direct patient interaction by a medical geneticist. Sources of information: A multidisciplinary team of nephrologists, genetic counselors, and medical geneticists developed an MGT pathway for ADPKD using current testing criteria for adult patient with suspected ADPKD and literature from MGT in oncology. Methods: An MGT pathway was assessed using a prospective cohort and compared to a retrospective cohort of 56 patients with ADPKD who received genetic testing using the standard, traditional pathway prior to implementing the MGT for ADPKD. The mainstream pathway was evaluated using time to diagnosis, diagnostic yield, and a patient survey to assess patient perceptions of the MGT pathway. Key findings: We assessed 26 patients with ADPKD using the MGT and 18 underwent genetic testing with return of results. Of them, 52 patients had data available for analysis in the traditional control cohort. The time for return of results using our MGT pathway was significantly shorter with a median time to results of 6 months compared to 12 months for the traditional pathway. We identified causative variants in 61% of patients, variants of uncertain significance in 28%, and 10% had negative testing which is in line with expectations from the literature. The patient surveys showed high satisfaction rates with the MGT pathway. Limitations: This report is an evaluation of a new genetic testing pathway restricted to a single, publicly funded health care center. The MGT pathway involved a prospective collection of a limited number of patients with ADPKD with comparison to a retrospective cohort of patients with ADPKD evaluated by standard testing. Implications: A MGT pathway using clearly defined criteria and commercially available gene panels for ADPKD can be successfully implemented in a publicly funded health care system to reduce the time required to obtain genetic results.

Evolving role of genetic testing for the clinical management of autosomal dominant polycystic kidney disease

2018 ◽  
Vol 34 (9) ◽  
pp. 1453-1460 ◽  
Author(s):  
Matthew B Lanktree ◽  
Ioan-Andrei Iliuta ◽  
Amirreza Haghighi ◽  
Xuewen Song ◽  
York Pei
Keyword(s):  
Genetic Testing ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Mutation Screening ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney

Abstract Autosomal dominant polycystic kidney disease (ADPKD) is caused primarily by mutations of two genes, PKD1 and PKD2. In the presence of a positive family history of ADPKD, genetic testing is currently seldom indicated as the diagnosis is mostly based on imaging studies using well-established criteria. Moreover, PKD1 mutation screening is technically challenging due to its large size, complexity (i.e. presence of six pseudogenes with high levels of DNA sequence similarity) and extensive allelic heterogeneity. Despite these limitations, recent studies have delineated a strong genotype–phenotype correlation in ADPKD and begun to unravel the role of genetics underlying cases with atypical phenotypes. Furthermore, adaptation of next-generation sequencing (NGS) to clinical PKD genetic testing will provide a high-throughput, accurate and comprehensive screen of multiple cystic disease and modifier genes at a reduced cost. In this review, we discuss the evolving indications of genetic testing in ADPKD and how NGS-based screening promises to yield clinically important prognostic information for both typical as well as unusual genetic (e.g. allelic or genic interactions, somatic mosaicism, cystic kidney disease modifiers) cases to advance personalized medicine in the era of novel therapeutics for ADPKD.

scholarly journals Combined Preimplantation Genetic Testing for Autosomal Dominant Polycystic Kidney Disease: Consequences for Embryos Available for Transfer

Genes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 692
Author(s):  
Pere Mir Pardo ◽  
José Antonio Martínez-Conejero ◽  
Julio Martín ◽  
Carlos Simón ◽  
Ana Cervero
Keyword(s):  
Genetic Testing ◽  
Kidney Disease ◽  
Male Infertility ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Polycystic Kidney ◽  
Male Factor ◽  
Preimplantation Genetic Testing ◽  
Female Age ◽  
Autosomal Dominant Polycystic Kidney

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and presents with genetic and clinical heterogeneity. ADPKD can also manifest extra-renally, and seminal cysts have been associated with male infertility in some cases. ADPKD-linked male infertility, along with female age, have been proposed as factors that may influence the clinical outcomes of preimplantation genetic testing (PGT) for monogenic disorders (PGT-M). Large PGT for aneuploidy assessment (PGT-A) studies link embryo aneuploidy to increasing female age; other studies suggest that embryo aneuploidy is also linked to severe male-factor infertility. We aimed to assess the number of aneuploid embryos and the number of cycles with transferable embryos in ADPKD patients after combined-PGT. The combined-PGT protocol, involving PGT-M by PCR and PGT-A by next-generation sequencing, was performed in single trophectoderm biopsies from 289 embryos in 83 PGT cycles. Transferable embryos were obtained in 69.9% of cycles. The number of aneuploid embryos and cycles with transferable embryos did not differ when the male or female had the ADPKD mutation. However, a significantly higher proportion of aneuploid embryos was found in the advanced maternal age (AMA) group, but not in the male factor (MF) group, when compared to non-AMA and non-MF groups, respectively. Additionally, no significant differences in the percentage of cycles with transferable embryos were found in any of the groups. Our results indicate that AMA couples among ADPKD patients have an increased risk of aneuploid embryos, but ADPKD-linked male infertility does not promote an increased aneuploidy rate.

scholarly journals The Kidney Genetics Clinic: delivering precision medicine for kidney patients

2021 ◽  
Vol 35 (3) ◽  
Author(s):  
Joaquim Calado ◽  
◽  
Rui Barata ◽  
Rita Lucas ◽  
Telma Francisco ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Kidney Disease ◽  
Tuberous Sclerosis ◽  
Polycystic Kidney Disease ◽  
Tuberous Sclerosis Complex ◽  
Autosomal Dominant ◽  
Molecular Testing ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney ◽  
The Impact

Molecular genetic testing in human traits has traditionally relied on affiliated academic facilities, been focused on specific phenotypes and supported by research funding. We report the experience of the Kidney Genetics Clinic (“consulta de Doenças Renais Hereditárias”) for the past 5 years, a period during which we have outsourced genetic testing. We evaluated the impact of molecular testing in patients’ care, but we also assessed disease‑specific imaging procedures and medicines provided. During the study period, 293 individuals were evaluated. Autosomal Dominant Polycystic Kidney Disease was the most frequent diagnosis (61.8%). In 125 patients, a genetic test was available, and for 76 of these (60.8%) a pathogenic/likely pathogenic variant was identified. Depend‑ ing on the phenotype, the mutation detection rate ranged from 100% (Tuberous Sclerosis Complex) to 15.4% (Autosomal Dominant Tubuloint‑ erstitial Kidney Disease). The impact of genetic testing on patients’ diagnosis and treatments is discussed. Total kidney volume was calculated in 6 patients with Autosomal Dominant Polycystic Kidney Disease and the combined volume for selected angiomyolipoma monitored in 3 individuals with the Tuberous Sclerosis Complex. Currently, 4 patients are being treated with Everolimus/Votubia™, 3 with Eculizumab/Soliris™ and 2 with Tolvaptan/Jinarc™. Our results demonstrate the feasibility of genetic molecular testing in a clinical setting while relying on outsourced sites for gene testing. We emphasize that it was only because the Kidney Genetics Clinic was given the opportunity to look after several patients affected by the same specific orphan or rare diseases (cohort enrichment) that we were able to improve diagnostic skills and deliver personalized medicines.

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