ReviewGenome medicine2022
A guide for the diagnosis of rare and undiagnosed disease: beyond the exome.
Review in Genome medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 213 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
213 citing papers in PubMed, 4 syntheses or guidelines pooled it, 363 citations in OpenAlex.
- Diagnostic yield of long-read sequencing for rare diseases: a systematic review.Frontiers in genetics · 2026Pooled it
- Genetic testing for diagnosing neurodevelopmental disorders and epilepsy: a systematic review and meta-analysis.Systematic reviews · 2025Pooled it
- A systematic review of hereditary neurological disorders diagnosed by whole exome sequencing in Pakistani population: updates from 2014 to November 2024.Neurogenetics · 2025Pooled it
- A Comprehensive Approach to the Diagnosis of Leigh Syndrome Spectrum.Diagnostics (Basel, Switzerland) · 2024Guideline
- The Korean Genetic Diagnosis Program for Rare Disease Phase II: outcomes of a 6-year national project.European journal of human genetics : EJHG · 2023Trial
- Current translational perspectives for diagnosis and individualized therapy in rare genetic diseases.Communications medicine · 2026Review
- Detecting pathogenic structural variation in families with undiagnosed rare disease in a national genome project.European journal of human genetics : EJHG · 2026Article
- PhenoSS: phenotype semantic similarity-based approach for rare disease prediction and patient clustering.Journal of the American Medical Informatics Association : JAMIA · 2026Article
- Practical approach to the diagnosis, management, and treatment of pediatric patients with bone fragility: an expert opinion.Journal of endocrinological investigation · 2026Review
- Pangenomes aid accurate detection of large insertions and deletions from targeted sequencing: the case of cardiomyopathies.Genome medicine · 2026Article
- Diagnostic delay, care needs, and trust in healthcare among persons with rare disease and their next of kin living in Sweden.Journal of community genetics · 2026Article
- Long-read sequencing for neurological disorders: opportunities, challenges, and future directions.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- Deciding "what" to screen for and "when": The importance of natural history information.American journal of human genetics · 2026Review
- Variant-specific RNA testing resolves variants of uncertain significance in exome testing.BMC genomics · 2026Article
- Parents' Perspectives on Access to Pediatric Rare Disease Cross-Border Clinical Trials in Europe: Experiences of Language Inclusion and Preferences.Therapeutic innovation & regulatory science · 2026Article
- Content validity, face validity and comprehensiveness of generic quality-of-life measures in adults and children with rare genetic conditions and their carers: a think aloud qualitative study.Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation · 2026Article
- Cell type-specific contextualisation of the human phenome: towards the systematic treatment of all rare diseases.Genome medicine · 2026Article
- Implementation of a medical genomics program for rare diseases in Uruguay.Orphanet journal of rare diseases · 2026Article
- Quality and consistency of genetic newborn screening reports in China: insights from a multi-laboratory analysis using simulated samples.BMC pediatrics · 2026Article
- Personalized Treatment in Rare Genetic Syndromes: A Case-Report in Witteveen-Kolk Syndrome (SIN3A).Molecular syndromology · 2026Article
153 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Rare diseases affect 30 million people in the USA and more than 300-400 million worldwide, often causing chronic illness, disability, and premature death. Traditional diagnostic techniques rely heavily on heuristic approaches, coupling clinical experience from prior rare disease presentations with the medical literature. A large number of rare disease patients remain undiagnosed for years and many even die without an accurate diagnosis. In recent years, gene panels, microarrays, and exome sequencing have helped to identify the molecular cause of such rare and undiagnosed diseases. These technologies have allowed diagnoses for a sizable proportion (25-35%) of undiagnosed patients, often with actionable findings. However, a large proportion of these patients remain undiagnosed. In this review, we focus on technologies that can be adopted if exome sequencing is unrevealing. We discuss the benefits of sequencing the whole genome and the additional benefit that may be offered by long-read technology, pan-genome reference, transcriptomics, metabolomics, proteomics, and methyl profiling. We highlight computational methods to help identify regionally distant patients with similar phenotypes or similar genetic mutations. Finally, we describe approaches to automate and accelerate genomic analysis. The strategies discussed here are intended to serve as a guide for clinicians and researchers in the next steps when encountering patients with non-diagnostic exomes.
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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.