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A practical approach to the genomics of kidney disorders

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Abstract

Rapid technological advances in genomic testing continue to increase our understanding of the genetic basis of a wide range of kidney disorders. Establishing a molecular diagnosis benefits the individual by bringing an end to what is often a protracted diagnostic odyssey, facilitates accurate reproductive counselling for families and, in the future, is likely to lead to the delivery of more targeted management and surveillance regimens. The selection of the most appropriate testing modality requires an understanding both of the technologies available and of the genetic architecture and heterogeneity of kidney disease. Whilst we are witnessing a far greater diagnostic yield with broader genetic testing, such approaches invariably generate variants of uncertain significance and secondary incidental findings, which are not only difficult to interpret but present ethical challenges with reporting and feeding back to patients and their families. Here, we review the spectrum of nephrogenetic disorders, consider the optimal approach to genetic testing, explore the clinical utility of obtaining a molecular diagnosis, reflect on the challenges of variant interpretation and look to the future of this dynamic field.

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Authors and Affiliations

  1. Department of Clinical Genetics, Great Ormond Street Hospital, London, UK

    Eleanor Hay & Angela Barnicoat

  2. North Thames Genomic Laboratory Hub, Great Ormond Street Hospital, London, UK

    Thomas Cullup

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AB and EH led the review and performed the literature search. AB, EH and TC contributed to the writing of the manuscript and EH takes responsibility for the content

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Hay, E., Cullup, T. & Barnicoat, A. A practical approach to the genomics of kidney disorders. Pediatr Nephrol 37, 21–35 (2022). https://doi.org/10.1007/s00467-021-04995-z

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