Genetic testing in the diagnosis of chronic kidney disease: recommendations for clinical practice

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

The overall diagnostic yield of massively parallel sequencing (MPS) based-tests in patients with chronic kidney disease (CKD) is around 30% for pediatric cases and 6-30% for adult cases. These figures should encourage nephrologists to frequently use genetic testing as a diagnostic means for their patients, but in reality several barriers appear to hinder the implementation of NGS diagnostics in routine clinical practice. In this paper, we aim to support the nephrologist to overcome these barriers. After a detailed discussion on the general items that are important to genetic testing in nephrology, namely (1) genetic testing modalities and their indications, (2) clinical information needed for high-quality interpretation of the genetic test, (3) clinical benefit of genetic testing and (4) genetic counselling, we will describe each of these items more specifically for the different groups of genetic kidney diseases and for CKD of unknown origin.

Related collections

Most cited references 120

Record: found
Abstract: found
Article: not found

Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology

Sue Richards, Nazneen Aziz, Sherri Bale … (2015)

The American College of Medical Genetics and Genomics (ACMG) previously developed guidance for the interpretation of sequence variants. 1 In the past decade, sequencing technology has evolved rapidly with the advent of high-throughput next generation sequencing. By adopting and leveraging next generation sequencing, clinical laboratories are now performing an ever increasing catalogue of genetic testing spanning genotyping, single genes, gene panels, exomes, genomes, transcriptomes and epigenetic assays for genetic disorders. By virtue of increased complexity, this paradigm shift in genetic testing has been accompanied by new challenges in sequence interpretation. In this context, the ACMG convened a workgroup in 2013 comprised of representatives from the ACMG, the Association for Molecular Pathology (AMP) and the College of American Pathologists (CAP) to revisit and revise the standards and guidelines for the interpretation of sequence variants. The group consisted of clinical laboratory directors and clinicians. This report represents expert opinion of the workgroup with input from ACMG, AMP and CAP stakeholders. These recommendations primarily apply to the breadth of genetic tests used in clinical laboratories including genotyping, single genes, panels, exomes and genomes. This report recommends the use of specific standard terminology: ‘pathogenic’, ‘likely pathogenic’, ‘uncertain significance’, ‘likely benign’, and ‘benign’ to describe variants identified in Mendelian disorders. Moreover, this recommendation describes a process for classification of variants into these five categories based on criteria using typical types of variant evidence (e.g. population data, computational data, functional data, segregation data, etc.). Because of the increased complexity of analysis and interpretation of clinical genetic testing described in this report, the ACMG strongly recommends that clinical molecular genetic testing should be performed in a CLIA-approved laboratory with results interpreted by a board-certified clinical molecular geneticist or molecular genetic pathologist or equivalent.

0 comments Cited 7488 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics.

Sarah S Kalia, Kathy Adelman, Sherri J. Bale … (2017)

Disclaimer: These recommendations are designed primarily as an educational resource for medical geneticists and other healthcare providers to help them provide quality medical services. Adherence to these recommendations is completely voluntary and does not necessarily assure a successful medical outcome. These recommendations should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed toward obtaining the same results. In determining the propriety of any specific procedure or test, the clinician should apply his or her own professional judgment to the specific clinical circumstances presented by the individual patient or specimen. Clinicians are encouraged to document the reasons for the use of a particular procedure or test, whether or not it is in conformance with this statement. Clinicians also are advised to take notice of the date this statement was adopted and to consider other medical and scientific information that becomes available after that date. It also would be prudent to consider whether intellectual property interests may restrict the performance of certain tests and other procedures.To promote standardized reporting of actionable information from clinical genomic sequencing, in 2013, the American College of Medical Genetics and Genomics (ACMG) published a minimum list of genes to be reported as incidental or secondary findings. The goal was to identify and manage risks for selected highly penetrant genetic disorders through established interventions aimed at preventing or significantly reducing morbidity and mortality. The ACMG subsequently established the Secondary Findings Maintenance Working Group to develop a process for curating and updating the list over time. We describe here the new process for accepting and evaluating nominations for updates to the secondary findings list. We also report outcomes from six nominations received in the initial 15 months after the process was implemented. Applying the new process while upholding the core principles of the original policy statement resulted in the addition of four genes and removal of one gene; one gene did not meet criteria for inclusion. The updated secondary findings minimum list includes 59 medically actionable genes recommended for return in clinical genomic sequencing. We discuss future areas of focus, encourage continued input from the medical community, and call for research on the impact of returning genomic secondary findings.Genet Med 19 2, 249-255.

0 comments Cited 408 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: not found
Article: not found

Atypical hemolytic-uremic syndrome.

Marina Noris, Giuseppe Remuzzi (2009)

0 comments Cited 339 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Title: Nephrology Dialysis Transplantation

Publisher: Oxford University Press (OUP)

ISSN (Print): 0931-0509

ISSN (Electronic): 1460-2385

Publication date Created: July 15 2021

Publication date (Electronic): July 15 2021

Affiliations

[1 ]Department of Genetics, University Medical Centre Groningen, The Netherlands

[2 ]Institut Imagine (Inserm U1163) et Département de Génétique, 24 bd du Montparnasse, 75015, Paris, France

[3 ]Medizinische Genetik Mainz, Limbach Genetics, Mainz, Germany

[4 ]Department of Medicine, Nephrology, University Hospital Freiburg, Germany

[5 ]Division of Nephrology, Cliniques Universitaires Saint-Luc, Avenue Hippocrate, 10, B-1200, Brussels, Belgium

[6 ]Center of Human Genetics, Institut de Pathologie et de Génétique, Avenue Lemaître, 25, B-6041, Gosselies, Belgium

[7 ]Unit of Medical Genetics, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy

[8 ]Department of Clinical and Experimental Biomedical Sciences “Mario Serio”, University of Florence, Florence, Italy

[9 ]Service de Néphrologie Pédiatrique, Hôpital Universitaire Necker-Enfants Malades, 149 rue de Sèvres, 75743, Paris, Cedex 15, France

[10 ]BSL-Z – ORCID 0000-0002-4169-9685, Centre for Rare Diseases, Medical University of Gdansk, Gdansk, Poland

[11 ]Clinical Genetics Unit, Department of Biology and Medical Genetics, Medical University of Gdansk, Gdansk, Poland

[12 ]Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Aldo & Cele Daccò Clinical Research Center for Rare Diseases, Bergamo, Italy

[13 ]Département de Génétique, Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75908, Paris, Cedex 15, France

[14 ]Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, University of Heidelberg, Germany

Article

DOI: 10.1093/ndt/gfab218

SO-VID: fa055558-e13a-489a-9fe6-90a6ac5c1cf2

License:

http://creativecommons.org/licenses/by-nc/4.0/

History

Data availability:

Comments

Comment on this article

scite_

Cited by 31

See all cited by

Most referenced authors 2,764

See all reference authors

- Version 1

Genetic testing in the diagnosis of chronic kidney disease: recommendations for clinical practice

Read this article at

Abstract

Related collections

Citation Behaviour and Practice

Most cited references 120

Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology

Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics.

Atypical hemolytic-uremic syndrome.

Author and article information

Journal

Affiliations

Article

History

Comments

Comment on this article

Similar content 396

Cited by 31

Most referenced authors 2,764