A targeted gene panel illuminates pathogenesis in young people with unexplained kidney failure.
Gene panel
Next generation sequencing
R257
Unexplained paediatric kidney failure
Journal
Journal of nephrology
ISSN: 1724-6059
Titre abrégé: J Nephrol
Pays: Italy
ID NLM: 9012268
Informations de publication
Date de publication:
05 Jun 2024
05 Jun 2024
Historique:
received:
22
05
2023
accepted:
26
04
2024
medline:
5
6
2024
pubmed:
5
6
2024
entrez:
5
6
2024
Statut:
aheadofprint
Résumé
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. 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. 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). 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.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 38837003
doi: 10.1007/s40620-024-01964-1
pii: 10.1007/s40620-024-01964-1
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Nephrotic syndrome trust
ID : Medical Research Council precision medicine grant MR/R013942
Organisme : Medical Research Council
ID : MR/Y008340/1
Pays : United Kingdom
Investigateurs
Charlotte Bebb
(C)
Fiona Beecroft
(F)
Emma Burkitt
(E)
Deirdre Cilliers
(D)
Abhijit Dixit
(A)
Jack Galliford
(J)
Wesley Hayes
(W)
Katherine A Hillman
(KA)
Richard Holt
(R)
Joanna Jarvis
(J)
Caroline Jones
(C)
Arveen Kamath
(A)
Mira Kharbanda
(M)
Alison Kraus
(A)
Rajesh Krishnan
(R)
Harry Leitch
(H)
Kay Metcalfe
(K)
Mordi Muorah
(M)
Nicholas Plant
(N)
Mohan Shenoy
(M)
Helen M Stuart
(HM)
Judith Van Der Voort
(J)
Emma Wakeling
(E)
Denise Williams
(D)
Informations de copyright
© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.
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