ArticleNPJ genomic medicine2023
Atypical splicing variants in PKD1 explain most undiagnosed typical familial ADPKD.
Article in NPJ genomic medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Diagnostic yield of long-read sequencing for rare diseases: a systematic review.Frontiers in genetics · 2026Pooled it
- Long-Read Sequencing in CKD Diagnostics: Breaking Genomic Barriers and Expanding Global Inclusion.Kidney international reports · 2026Review
- 'Missing' disease-causing variants in Alport syndrome.Nature reviews. Nephrology · 2026Review
- Caring for Australians and New ZealandeRs with kidney Impairment guideline commentary on kidney disease: improving global outcomes 2025 guidelines for diagnosis and management of autosomal polycystic kidney disease.Internal medicine journal · 2026Article
- Monogenic kidney disease and monogenic diabetes are present in renal clinic patients with non-genetic diagnoses.Scientific reports · 2026Article
- Genomic and epigenomic landscape of ADPKD: towards precision diagnostics and tailored treatments.Frontiers in epigenetics and epigenomics · 2026Review
- PKD1 5'UTR variants are a rare cause of disease in ADPKD and suggest a new focus for therapeutic development.European journal of human genetics : EJHG · 2026Article
- Case Report: Functional validation of aFrontiers in genetics · 2026Article
- Autosomal dominant polycystic kidney disease: an overview of recent genetic and clinical advances.Renal failure · 2025Review
- Data-driven insights to inform splice-altering variant assessment.American journal of human genetics · 2025Article
- Coexisting genetic kidney disease explains many cases of 'familial' IgA nephropathy where the proband has biopsy-confirmed mesangial IgA deposits.Frontiers in medicine · 2025Article
- Somatic mutation in autosomal dominant polycystic kidney disease revealed by deep sequencing human kidney cysts.NPJ genomic medicine · 2024Article
- Quantifying variant contributions in cystic kidney disease using national-scale whole-genome sequencing.The Journal of clinical investigation · 2024Article
- Refining clinically relevant parameters for mis-splicing risk in shortened introns with donor-to-branchpoint space constraint.European journal of human genetics : EJHG · 2024Article
- Exploring the impact and utility of genomic sequencing in established CKD.Clinical kidney journal · 2024Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of kidney failure and is primarily associated with PKD1 or PKD2. Approximately 10% of patients remain undiagnosed after standard genetic testing. We aimed to utilise short and long-read genome sequencing and RNA studies to investigate undiagnosed families. Patients with typical ADPKD phenotype and undiagnosed after genetic diagnostics were recruited. Probands underwent short-read genome sequencing, PKD1 and PKD2 coding and non-coding analyses and then genome-wide analysis. Targeted RNA studies investigated variants suspected to impact splicing. Those undiagnosed then underwent Oxford Nanopore Technologies long-read genome sequencing. From over 172 probands, 9 met inclusion criteria and consented. A genetic diagnosis was made in 8 of 9 (89%) families undiagnosed on prior genetic testing. Six had variants impacting splicing, five in non-coding regions of PKD1. Short-read genome sequencing identified novel branchpoint, AG-exclusion zone and missense variants generating cryptic splice sites and a deletion causing critical intron shortening. Long-read sequencing confirmed the diagnosis in one family. Most undiagnosed families with typical ADPKD have splice-impacting variants in PKD1. We describe a pragmatic method for diagnostic laboratories to assess PKD1 and PKD2 non-coding regions and validate suspected splicing variants through targeted RNA studies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.