ArticleGenome medicine2023
Beyond the exome: utility of long-read whole genome sequencing in exome-negative autosomal recessive diseases.
Article in Genome medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Diagnostic yield of long-read sequencing for rare diseases: a systematic review.Frontiers in genetics · 2026Pooled it
- Clinical Epigenomics in Rare Diseases: Interpreting DNA Methylation Episignatures.Molecular genetics & genomic medicine · 2026Review
- Review
- Unraveling missing variants through target capture-based long-read sequencing in autosomal recessive disorders.European journal of human genetics : EJHG · 2026Article
- Systematic evaluation of long-read and short-read sequencing in neurological disorders diagnosis: a direct comparison study of 310 patients.NPJ genomic medicine · 2026Article
- Sensitivity of HiFi long-read genome sequencing for difficult-to-detect pathogenic variants when applied to real-world clinical laboratory samples.American journal of human genetics · 2026Article
- Completely resolved structural variants by optical genome mapping with adaptive sampling from CNV discovery.NPJ genomic medicine · 2026Article
- Long-read Sequencing in Inherited Retinal Dystrophies: A Systematic Review.Ophthalmology science · 2026Review
- Addressing the diagnostic gap through deep phenotyping.Human genomics · 2026Article
- Benchmarking long-read variant calling in diploid and polyploid genomes: insights from human and plants.BMC genomics · 2026Article
- Juvenile-Onset Cerebrotendinous Xanthomatosis with Novel Compound Heterozygous CYP27A1 Mutations: Case Series and Literature Review.Cerebellum (London, England) · 2026Review
- Genomics in Health and Biomedicine.Advances in experimental medicine and biology · 2026Review
- Strawberry atlas:PeerJ · 2026Article
- Long-read sequencing identifies a novel de novo inversion in SMARCC2 in a pediatric patient with Coffin-siris syndrome 8: a case report.BMC medical genomics · 2025Article
- Mitochondrial Macular Dystrophy-A Case Report and Mini Review of Retinal Dystrophies.Journal of clinical medicine · 2025Article
- Oxford Nanopore Technologies [ONT] Sequencing: Clinical Validation in Genetically Heterogeneous Disorders.Genes · 2025Article
- GREGoR: accelerating genomics for rare diseases.Nature · 2025Article
- Long read whole genome sequencing-based discovery of structural variants and their role in aetiology of non-syndromic autism spectrum disorder in India.BMC medical genomics · 2025Article
- The additional diagnostic yield of long-read sequencing in undiagnosed rare diseases.Genome research · 2025Review
- Non-histone lactylation: unveiling its functional significance.Frontiers in cell and developmental biology · 2025Review
Corrections and comments
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Authors and funding
39 authors at 9 institutions in 2 countries.
Funding
Abstract
backgroundLong-read whole genome sequencing (lrWGS) has the potential to address the technical limitations of exome sequencing in ways not possible by short-read WGS. However, its utility in autosomal recessive Mendelian diseases is largely unknown.
methodsIn a cohort of 34 families in which the suspected autosomal recessive diseases remained undiagnosed by exome sequencing, lrWGS was performed on the Pacific Bioscience Sequel IIe platform.
resultsLikely causal variants were identified in 13 (38%) of the cohort. These include (1) a homozygous splicing SV in TYMS as a novel candidate gene for lethal neonatal lactic acidosis, (2) a homozygous non-coding SV that we propose impacts STK25 expression and causes a novel neurodevelopmental disorder, (3) a compound heterozygous SV in RP1L1 with complex inheritance pattern in a family with inherited retinal disease, (4) homozygous deep intronic variants in LEMD2 and SNAP91 as novel candidate genes for neurodevelopmental disorders in two families, and (5) a promoter SNV in SLC4A4 causing non-syndromic band keratopathy. Surprisingly, we also encountered causal variants that could have been identified by short-read exome sequencing in 7 families. The latter highlight scenarios that are especially challenging at the interpretation level.
conclusionsOur data highlight the continued need to address the interpretation challenges in parallel with efforts to improve the sequencing technology itself. We propose a path forward for the implementation of lrWGS sequencing in the setting of autosomal recessive diseases in a way that maximizes its utility.
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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.