ArticleGenetics in medicine : official journal of the American College of Medical Genetics2024
Narrowing the diagnostic gap: Genomes, episignatures, long-read sequencing, and health economic analyses in an exome-negative intellectual disability cohort.
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Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
4.4field-weighted citation impact, top 6% of its field
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.
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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.
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Who cites it
10 citing papers in PubMed, 8 citations in OpenAlex.
- A nationwide prospective randomized trial for diagnosing developmental disorders demonstrates genome sequencing outperforms standard of care.Genome medicine · 2026Trial
- Review
- Structural variant discovery and diagnostic impact in rare diseases from short-read and long-read sequencing.medRxiv : the preprint server for health sciences · 2026Article
- Diagnostic Yield of Genome Sequencing in an Iranian Exome-Negative Autosomal-Recessive Intellectual Disability Cohort.Human mutation · 2026Article
- GREGoR: accelerating genomics for rare diseases.Nature · 2025Article
- GREGoR: Accelerating Genomics for Rare Diseases.ArXiv · 2024Article
- Considerations for reporting variants in novel candidate genes identified during clinical genomic testing.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Considerations for reporting variants in novel candidate genes identified during clinical genomic testing.bioRxiv : the preprint server for biology · 2024Article
- Clinician-Driven Reanalysis of Exome Sequencing Data From Patients With Inherited Retinal Diseases.JAMA network open · 2024Article
- Phenotypic compatibility and specificity in genomic variant classification.European journal of human genetics : EJHG · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
65 authors at 20 institutions in 4 countries.
Kerith-Rae DiasNeuroscience Research Australia, Sydney, NSW, Australia; Prince of Wales Clinical School, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.
Rupendra ShresthaCentre for Economic Impacts of Genomic Medicine, Macquarie Business School, Macquarie University, Sydney, NSW, Australia.
Deborah SchofieldCentre for Economic Impacts of Genomic Medicine, Macquarie Business School, Macquarie University, Sydney, NSW, Australia.
Carey-Anne EvansNeuroscience Research Australia, Sydney, NSW, Australia; New South Wales Health Pathology Randwick Genomics, Prince of Wales Hospital, Sydney, NSW, Australia.
Emily O'HeirProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
Ying ZhuNeuroscience Research Australia, Sydney, NSW, Australia; New South Wales Health Pathology Randwick Genomics, Prince of Wales Hospital, Sydney, NSW, Australia; The Genetics of Learning Disability Service, Waratah, NSW, Australia.
Futao ZhangNeuroscience Research Australia, Sydney, NSW, Australia; New South Wales Health Pathology Randwick Genomics, Prince of Wales Hospital, Sydney, NSW, Australia.
Krystle StandenNew South Wales Health Pathology Randwick Genomics, Prince of Wales Hospital, Sydney, NSW, Australia.
Ben WeisburdProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
Sarah L StentonProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
Alba Sanchis-JuanProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
Harrison BrandProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
Michael E TalkowskiProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
Alan MaDepartment of Clinical Genetics, Children's Hospital at Westmead, Sydney Children's Hospital Network, Sydney, NSW, Australia; Specialty of Genomic Medicine, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
Sondy GhediaDepartment of Clinical Genetics, Royal North Shore Hospital, Sydney, NSW, Australia; Northern Clinical School, Royal North Shore Hospital, Sydney, NSW, Australia.
Meredith WilsonDepartment of Clinical Genetics, Children's Hospital at Westmead, Sydney Children's Hospital Network, Sydney, NSW, Australia.
Sarah A SandaraduraDepartment of Clinical Genetics, Children's Hospital at Westmead, Sydney Children's Hospital Network, Sydney, NSW, Australia; Disciplines of Child and Adolescent Health and Genetic Medicine, University of Sydney, Sydney, NSW 2050, Australia.
Janine SmithDepartment of Clinical Genetics, Children's Hospital at Westmead, Sydney Children's Hospital Network, Sydney, NSW, Australia; Specialty of Genomic Medicine, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
Benjamin KamienGenetic Services of Western Australia, Perth, WA, Australia; School of Paediatrics and Child Health, University of Western Australia, Perth, WA, Australia.
Anne TurnerCentre for Clinical Genetics, Sydney Children's Hospital, Sydney, NSW, Australia.
Madhura BakshiDepartment of Clinical Genetics, Liverpool Hospital, Sydney, NSW, Australia.
Lesley C AdèsDepartment of Clinical Genetics, Children's Hospital at Westmead, Sydney Children's Hospital Network, Sydney, NSW, Australia; Disciplines of Child and Adolescent Health and Genetic Medicine, University of Sydney, Sydney, NSW 2050, Australia.
David MowatCentre for Clinical Genetics, Sydney Children's Hospital, Sydney, NSW, Australia; Discipline of Paediatrics & Child Health, Faculty of Medicine and Health, School of Clinical Medicine, University of New South Wales, Sydney, NSW, Australia.
Matthew ReganMonash Genetics, Monash Health, Melbourne, VIC, Australia.
George McGillivrayVictorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia.
Ravi SavarirayanVictorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia; Murdoch Children's Research Institute, Melbourne, VIC, Australia; Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia.
Susan M WhiteVictorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia; Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia.
Tiong Yang TanVictorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia; Murdoch Children's Research Institute, Melbourne, VIC, Australia; Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia.
Zornitza StarkVictorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia; Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia; Australian Genomics, Melbourne, VIC, Australia.
Natasha J BrownVictorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia; Murdoch Children's Research Institute, Melbourne, VIC, Australia; Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia.
Luis A Pérez-JuradoGenetics Unit, Universitat Pompeu Fabra, Institut Hospital del Mar d'Investigacions Mediques (IMIM), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain; Women's and Children's Hospital, South Australian Health and Medical Research Institute & University of Adelaide, Adelaide, SA, Australia.
Emma KrzesinskiMonash Genetics, Monash Health, Melbourne, VIC, Australia; Department of Paediatrics, Monash University, Melbourne, VIC, Australia.
Matthew F HunterMonash Genetics, Monash Health, Melbourne, VIC, Australia; Department of Paediatrics, Monash University, Melbourne, VIC, Australia.
Lauren AkessonMelbourne Pathology, Melbourne, VIC, Australia; Department of Pathology, The Royal Melbourne Hospital, Melbourne, VIC, Australia; Melbourne Medical School, University of Melbourne, Melbourne, VIC, Australia.
Andrew Paul FennellMonash Genetics, Monash Health, Melbourne, VIC, Australia; Department of Paediatrics, Monash University, Melbourne, VIC, Australia.
Alison YeungVictorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia; Murdoch Children's Research Institute, Melbourne, VIC, Australia; Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia.
Tiffany BoughtwoodMurdoch Children's Research Institute, Melbourne, VIC, Australia; Australian Genomics, Melbourne, VIC, Australia.
Lisa J EwansCentre for Clinical Genetics, Sydney Children's Hospital, Sydney, NSW, Australia; Discipline of Paediatrics & Child Health, Faculty of Medicine and Health, School of Clinical Medicine, University of New South Wales, Sydney, NSW, Australia; Genomics and Inherited Disease Program, Garvan Institute of Medical Research, University of New South Wales Sydney, Sydney, NSW, Australia.
Jennifer KerkhofVerspeeten Clinical Genome Centre London Health Sciences Centre, London, ON, Canada.
Christopher LucasNew South Wales Health Pathology Randwick Genomics, Prince of Wales Hospital, Sydney, NSW, Australia.
Louise CareyNew South Wales Health Pathology Randwick Genomics, Prince of Wales Hospital, Sydney, NSW, Australia.
Hugh FrenchDepartment of Medical Genomics, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
Melissa RapadasGenomics and Inherited Disease Program, Garvan Institute of Medical Research, University of New South Wales Sydney, Sydney, NSW, Australia; Centre for Population Genomics, Garvan Institute of Medical Research and Murdoch Children's Research Institute, Sydney, NSW, Australia.
Igor StevanovskiGenomics and Inherited Disease Program, Garvan Institute of Medical Research, University of New South Wales Sydney, Sydney, NSW, Australia; Centre for Population Genomics, Garvan Institute of Medical Research and Murdoch Children's Research Institute, Sydney, NSW, Australia.
Ira W DevesonGenomics and Inherited Disease Program, Garvan Institute of Medical Research, University of New South Wales Sydney, Sydney, NSW, Australia; Centre for Population Genomics, Garvan Institute of Medical Research and Murdoch Children's Research Institute, Sydney, NSW, Australia; St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
Corrina CliffeNew South Wales Health Pathology Randwick Genomics, Prince of Wales Hospital, Sydney, NSW, Australia.
George ElakisNew South Wales Health Pathology Randwick Genomics, Prince of Wales Hospital, Sydney, NSW, Australia.
Edwin P KirkNew South Wales Health Pathology Randwick Genomics, Prince of Wales Hospital, Sydney, NSW, Australia; Centre for Clinical Genetics, Sydney Children's Hospital, Sydney, NSW, Australia; Discipline of Paediatrics & Child Health, Faculty of Medicine and Health, School of Clinical Medicine, University of New South Wales, Sydney, NSW, Australia.
Tracy Dudding-BythThe Genetics of Learning Disability Service, Waratah, NSW, Australia.
Janice FletcherNew South Wales Health Pathology Randwick Genomics, Prince of Wales Hospital, Sydney, NSW, Australia.
Rebecca WalshNew South Wales Health Pathology Randwick Genomics, Prince of Wales Hospital, Sydney, NSW, Australia.
Mark A CorbettAdelaide Medical School and Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia.
Thessa KroesAdelaide Medical School and Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia.
Jozef GeczAdelaide Medical School and Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia; South Australian Health and Medical Research Institute, Adelaide, SA, Australia.
Cliff MeldrumState Wide Service, New South Wales Health Pathology, Sydney, NSW, Australia.
Simon CliffeState Wide Service, New South Wales Health Pathology, Sydney, NSW, Australia.
Meg WallVictorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia.
Sebastian LunkeVictorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia.
Kathryn NorthMurdoch Children's Research Institute, Melbourne, VIC, Australia; Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia; Australian Genomics, Melbourne, VIC, Australia; Global Alliance for Genomics and Health, Toronto, ON, Canada.
David J AmorMurdoch Children's Research Institute, Melbourne, VIC, Australia; Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia.
Michael FieldThe Genetics of Learning Disability Service, Waratah, NSW, Australia.
Bekim SadikovicVerspeeten Clinical Genome Centre London Health Sciences Centre, London, ON, Canada; Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada.
Michael F BuckleyNew South Wales Health Pathology Randwick Genomics, Prince of Wales Hospital, Sydney, NSW, Australia.
Anne O'Donnell-LuriaProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA.
Tony RoscioliNeuroscience Research Australia, Sydney, NSW, Australia; Prince of Wales Clinical School, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia; New South Wales Health Pathology Randwick Genomics, Prince of Wales Hospital, Sydney, NSW, Australia. Electronic address: tony.roscioli@health.nsw.gov.au.
Prince of Wales Hospital · AUBroad Institute · USNew South Wales Department of Health · AUThe University of Melbourne · AUMonash Health · AUThe University of Sydney · AUVictorian Clinical Genetics Services · AUGarvan Institute of Medical Research · AUHunter Genetics · AUMacquarie University · AUThe University of Adelaide · AUChildren's Hospital at Westmead · AULiverpool Hospital · AULondon Health Sciences Centre · CAMurdoch Children's Research Institute · AUOntario Genomics · CARoyal North Shore Hospital · AURoyal Prince Alfred Hospital · AUSouth Australian Health and Medical Research Institute · AUSydney Children's Hospital · AU
Funding
Broad Institute Mendelian Genomic Research CenterU01HG011755 · NHGRI · BROAD INSTITUTE, INC. · PI Anne O'Donnell-Luria, MICHAEL E TALKOWSKI · 2021 to 2026
$14.6MScalable tool and comprehensive maps to interpret structural variation across the neuropsychiatric spectrumR01MH115957 · NIMH · BROAD INSTITUTE, INC. · PI TALKOWSKI, MICHAEL E · 2019 to 2025
$5.4MA powerful web-based discovery platform for rare disease geneticsR01HG009141 · NHGRI · BROAD INSTITUTE, INC. · PI QUINLAN, AARON R, REHM, HEIDI L · 2017 to 2020
$2.9MNHGRI NIH HHS R01 HG009141NHGRI NIH HHS U01 HG011755NIMH NIH HHS R01 MH115957
Abstract
purposeGenome sequencing (GS)-specific diagnostic rates in prospective tightly ascertained exome sequencing (ES)-negative intellectual disability (ID) cohorts have not been reported extensively.
methodsES, GS, epigenetic signatures, and long-read sequencing diagnoses were assessed in 74 trios with at least moderate ID.
resultsThe ES diagnostic yield was 42 of 74 (57%). GS diagnoses were made in 9 of 32 (28%) ES-unresolved families. Repeated ES with a contemporary pipeline on the GS-diagnosed families identified 8 of 9 single-nucleotide variations/copy-number variations undetected in older ES, confirming a GS-unique diagnostic rate of 1 in 32 (3%). Episignatures contributed diagnostic information in 9% with GS corroboration in 1 of 32 (3%) and diagnostic clues in 2 of 32 (6%). A genetic etiology for ID was detected in 51 of 74 (69%) families. Twelve candidate disease genes were identified. Contemporary ES followed by GS cost US$4976 (95% CI: $3704; $6969) per diagnosis and first-line GS at a cost of $7062 (95% CI: $6210; $8475) per diagnosis.
conclusionPerforming GS only in ID trios would be cost equivalent to ES if GS were available at $2435, about a 60% reduction from current prices. This study demonstrates that first-line GS achieves higher diagnostic rate than contemporary ES but at a higher cost.
Indexed as
ExomeExome SequencingIntellectual DisabilityChildChild, PreschoolCohort StudiesDNA Copy Number VariationsFemaleGenetic TestingGenome, HumanHumansMalePolymorphism, Single NucleotideWhole Genome SequencingEpisignatureExome negativeGenome sequencingHealth economicsIntellectual disability
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