A targeted gene panel illuminates pathogenesis in young people with unexplained kidney failure.

Autor: Beal F; Paediatric Nephrology, Birmingham Children's Hospital, Steelhouse Lane, Birmingham, UK. felicity.beal@nhs.net., Forrester N; Bristol Genetics Laboratory, North Bristol NHS Trust, Southmead Hospital, Bristol, UK., Watson E; Bristol Genetics Laboratory, North Bristol NHS Trust, Southmead Hospital, Bristol, UK., Williams M; Bristol Genetics Laboratory, North Bristol NHS Trust, Southmead Hospital, Bristol, UK., Buckton A; Great Ormond Street Genetics Laboratory, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, UK., Marlais M; UCL Great Ormond Street Institute of Child Health, University College London, London, UK.; Paediatric Nephrology, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, UK., Maxted A; Paediatric Nephrology, Nottingham University Hospitals NHS Trust, Nottingham, UK., Woolf AS; Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester, UK.; Royal Manchester Children's Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK., Saleem MA; Paediatric Nephrology, Bristol Royal Hospital for Children, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK., Platt C; Paediatric Nephrology, Bristol Royal Hospital for Children, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK.
Jazyk: angličtina
Zdroj: Journal of nephrology [J Nephrol] 2024 Jun; Vol. 37 (5), pp. 1273-1284. Date of Electronic Publication: 2024 Jun 05.
DOI: 10.1007/s40620-024-01964-1
Abstrakt: Background: Kidney failure in young people is often unexplained and a significant proportion will have an underlying genetic diagnosis. National Health Service England pioneered a comprehensive genomic testing service for such circumstances accessible to clinicians working outside of genetics. This is the first review of patients using this novel service since October 2021, following its introduction into clinical practice.
Methods: The 'Unexplained Young-Onset End-Stage Renal Disease' (test-code R257) gene panel uses targeted next generation sequencing to analyse 175 genes associated with renal disease in patients under 36 years of age. All tests undertaken between October 2021 and February 2022 were reviewed. Phenotypic data were extracted from request forms and referring clinicians contacted where additional details were required.
Results: Seventy-one patients underwent R257 testing over the study period. Among them, 23/71 patients (32%) were confirmed to have a genetic diagnosis and 2/71 (3%) had a genetically suggestive variant. Nephronophthisis and Alport syndrome were the most common conditions identified, (4/23 (17%) with pathogenic variants in NPHP1 and 4/23 (17%) with pathogenic variants in COL4A3/COL4A4). Positive predictors of a genetic diagnosis included a family history of renal disease (60% of positive cases) and extra-renal disease manifestations (48% of positive cases).
Conclusion: This is the first study to evaluate the R257 gene panel in unexplained young-onset kidney failure, freely accessible to patients meeting testing criteria in England. A genetic diagnosis was identified in 32% of patients. This study highlights the essential and expanding role that genomic testing has for children and families affected by renal disease today.
(© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)
Databáze: MEDLINE
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