. 2024 May;26(5):101076.

doi: 10.1016/j.gim.2024.101076. Epub 2024 Jan 19.

Narrowing the diagnostic gap: Genomes, episignatures, long-read sequencing, and health economic analyses in an exome-negative intellectual disability cohort

Kerith-Rae Dias¹, Rupendra Shrestha², Deborah Schofield², Carey-Anne Evans³, Emily O'Heir⁴, Ying Zhu⁵, Futao Zhang³, Krystle Standen⁶, Ben Weisburd⁴, Sarah L Stenton⁴, Alba Sanchis-Juan⁴, Harrison Brand⁴, Michael E Talkowski⁴, Alan Ma⁷, Sondy Ghedia⁸, Meredith Wilson⁹, Sarah A Sandaradura¹⁰, Janine Smith⁷, Benjamin Kamien¹¹, Anne Turner¹², Madhura Bakshi¹³, Lesley C Adès¹⁰, David Mowat¹⁴, Matthew Regan¹⁵, George McGillivray¹⁶, Ravi Savarirayan¹⁷, Susan M White¹⁸, Tiong Yang Tan¹⁷, Zornitza Stark¹⁹, Natasha J Brown¹⁷, Luis A Pérez-Jurado²⁰, Emma Krzesinski²¹, Matthew F Hunter²¹, Lauren Akesson²², Andrew Paul Fennell²¹, Alison Yeung¹⁷, Tiffany Boughtwood²³, Lisa J Ewans²⁴, Jennifer Kerkhof²⁵, Christopher Lucas⁶, Louise Carey⁶, Hugh French²⁶, Melissa Rapadas²⁷, Igor Stevanovski²⁷, Ira W Deveson²⁸, Corrina Cliffe⁶, George Elakis⁶, Edwin P Kirk²⁹, Tracy Dudding-Byth³⁰, Janice Fletcher⁶, Rebecca Walsh⁶, Mark A Corbett³¹, Thessa Kroes³¹, Jozef Gecz³², Cliff Meldrum³³, Simon Cliffe³³, Meg Wall¹⁶, Sebastian Lunke¹⁶, Kathryn North³⁴, David J Amor³⁵, Michael Field³⁰, Bekim Sadikovic³⁶, Michael F Buckley⁶, Anne O'Donnell-Luria³⁷, Tony Roscioli³⁸

Affiliations

¹ Neuroscience Research Australia, Sydney, NSW, Australia; Prince of Wales Clinical School, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.
² Centre for Economic Impacts of Genomic Medicine, Macquarie Business School, Macquarie University, Sydney, NSW, Australia.
³ Neuroscience Research Australia, Sydney, NSW, Australia; New South Wales Health Pathology Randwick Genomics, Prince of Wales Hospital, Sydney, NSW, Australia.
⁴ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
⁵ Neuroscience 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.
⁶ New South Wales Health Pathology Randwick Genomics, Prince of Wales Hospital, Sydney, NSW, Australia.
⁷ Department 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.
⁸ Department of Clinical Genetics, Royal North Shore Hospital, Sydney, NSW, Australia; Northern Clinical School, Royal North Shore Hospital, Sydney, NSW, Australia.
⁹ Department of Clinical Genetics, Children's Hospital at Westmead, Sydney Children's Hospital Network, Sydney, NSW, Australia.
¹⁰ Department 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.
¹¹ Genetic Services of Western Australia, Perth, WA, Australia; School of Paediatrics and Child Health, University of Western Australia, Perth, WA, Australia.
¹² Centre for Clinical Genetics, Sydney Children's Hospital, Sydney, NSW, Australia.
¹³ Department of Clinical Genetics, Liverpool Hospital, Sydney, NSW, Australia.
¹⁴ 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.
¹⁵ Monash Genetics, Monash Health, Melbourne, VIC, Australia.
¹⁶ Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia.
¹⁷ Victorian 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.
¹⁸ Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia; Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia.
¹⁹ Victorian 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.
²⁰ Genetics 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.
²¹ Monash Genetics, Monash Health, Melbourne, VIC, Australia; Department of Paediatrics, Monash University, Melbourne, VIC, Australia.
²² Melbourne Pathology, Melbourne, VIC, Australia; Department of Pathology, The Royal Melbourne Hospital, Melbourne, VIC, Australia; Melbourne Medical School, University of Melbourne, Melbourne, VIC, Australia.
²³ Murdoch Children's Research Institute, Melbourne, VIC, Australia; Australian Genomics, Melbourne, VIC, Australia.
²⁴ 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; Genomics and Inherited Disease Program, Garvan Institute of Medical Research, University of New South Wales Sydney, Sydney, NSW, Australia.
²⁵ Verspeeten Clinical Genome Centre London Health Sciences Centre, London, ON, Canada.
²⁶ Department of Medical Genomics, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
²⁷ Genomics 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.
²⁸ Genomics 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.
²⁹ New 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.
³⁰ The Genetics of Learning Disability Service, Waratah, NSW, Australia.
³¹ Adelaide Medical School and Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia.
³² Adelaide Medical School and Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia; South Australian Health and Medical Research Institute, Adelaide, SA, Australia.
³³ State Wide Service, New South Wales Health Pathology, Sydney, NSW, Australia.
³⁴ Murdoch 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.
³⁵ Murdoch Children's Research Institute, Melbourne, VIC, Australia; Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia.
³⁶ Verspeeten Clinical Genome Centre London Health Sciences Centre, London, ON, Canada; Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada.
³⁷ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA.
³⁸ Neuroscience 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.

PMID: 38258669
PMCID: PMC11786952
DOI: 10.1016/j.gim.2024.101076

Narrowing the diagnostic gap: Genomes, episignatures, long-read sequencing, and health economic analyses in an exome-negative intellectual disability cohort

Kerith-Rae Dias et al. Genet Med. 2024 May.

. 2024 May;26(5):101076.

doi: 10.1016/j.gim.2024.101076. Epub 2024 Jan 19.

Authors

Affiliations

¹ Neuroscience Research Australia, Sydney, NSW, Australia; Prince of Wales Clinical School, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.
² Centre for Economic Impacts of Genomic Medicine, Macquarie Business School, Macquarie University, Sydney, NSW, Australia.
³ Neuroscience Research Australia, Sydney, NSW, Australia; New South Wales Health Pathology Randwick Genomics, Prince of Wales Hospital, Sydney, NSW, Australia.
⁴ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
⁵ Neuroscience 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.
⁶ New South Wales Health Pathology Randwick Genomics, Prince of Wales Hospital, Sydney, NSW, Australia.
⁷ Department 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.
⁸ Department of Clinical Genetics, Royal North Shore Hospital, Sydney, NSW, Australia; Northern Clinical School, Royal North Shore Hospital, Sydney, NSW, Australia.
⁹ Department of Clinical Genetics, Children's Hospital at Westmead, Sydney Children's Hospital Network, Sydney, NSW, Australia.
¹⁰ Department 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.
¹¹ Genetic Services of Western Australia, Perth, WA, Australia; School of Paediatrics and Child Health, University of Western Australia, Perth, WA, Australia.
¹² Centre for Clinical Genetics, Sydney Children's Hospital, Sydney, NSW, Australia.
¹³ Department of Clinical Genetics, Liverpool Hospital, Sydney, NSW, Australia.
¹⁴ 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.
¹⁵ Monash Genetics, Monash Health, Melbourne, VIC, Australia.
¹⁶ Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia.
¹⁷ Victorian 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.
¹⁸ Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia; Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia.
¹⁹ Victorian 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.
²⁰ Genetics 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.
²¹ Monash Genetics, Monash Health, Melbourne, VIC, Australia; Department of Paediatrics, Monash University, Melbourne, VIC, Australia.
²² Melbourne Pathology, Melbourne, VIC, Australia; Department of Pathology, The Royal Melbourne Hospital, Melbourne, VIC, Australia; Melbourne Medical School, University of Melbourne, Melbourne, VIC, Australia.
²³ Murdoch Children's Research Institute, Melbourne, VIC, Australia; Australian Genomics, Melbourne, VIC, Australia.
²⁴ 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; Genomics and Inherited Disease Program, Garvan Institute of Medical Research, University of New South Wales Sydney, Sydney, NSW, Australia.
²⁵ Verspeeten Clinical Genome Centre London Health Sciences Centre, London, ON, Canada.
²⁶ Department of Medical Genomics, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
²⁷ Genomics 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.
²⁸ Genomics 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.
²⁹ New 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.
³⁰ The Genetics of Learning Disability Service, Waratah, NSW, Australia.
³¹ Adelaide Medical School and Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia.
³² Adelaide Medical School and Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia; South Australian Health and Medical Research Institute, Adelaide, SA, Australia.
³³ State Wide Service, New South Wales Health Pathology, Sydney, NSW, Australia.
³⁴ Murdoch 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.
³⁵ Murdoch Children's Research Institute, Melbourne, VIC, Australia; Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia.
³⁶ Verspeeten Clinical Genome Centre London Health Sciences Centre, London, ON, Canada; Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada.
³⁷ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA.
³⁸ Neuroscience 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.

PMID: 38258669
PMCID: PMC11786952
DOI: 10.1016/j.gim.2024.101076

Abstract

Purpose: Genome sequencing (GS)-specific diagnostic rates in prospective tightly ascertained exome sequencing (ES)-negative intellectual disability (ID) cohorts have not been reported extensively.

Methods: ES, GS, epigenetic signatures, and long-read sequencing diagnoses were assessed in 74 trios with at least moderate ID.

Results: The 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.

Conclusion: Performing 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.

Keywords: Episignature; Exome negative; Genome sequencing; Health economics; Intellectual disability.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest The authors declare no conflicts of interest.

Figures

**Figure 1.. ID Flagship study.**
74 trios with molecularly undiagnosed ID investigated using ES (74 trios), GS (32 trios), EpiSign (32 probands) and LRS (16 probands). The overall ES/GS diagnostic yield is 69% (51/74) with 31% (23/74) unresolved. ID, intellectual disability; ES, exome sequencing, GS, genome sequencing; LRS, long read sequencing.

**Figure 2.. Concordance between GS and episignature findings.**
A. A Kleefstra syndrome episignature in proband 62 was concordant to the finding of a duplication in *EHMT1* using GS. B. A Beckwith-Weidemann syndrome with IC2 episignature in proband 44 and detection of a *de novo* heterozygous partial out of frame tandem duplication (NM_015335.5, exons 5 – 16 of 31) of *MED13L* using GS might be related by a yet unknown mechanism.

See this image and copyright information in PMC

Cited by

Phenotypic compatibility and specificity in genomic variant classification.
Basel-Salmon L. Basel-Salmon L. Eur J Hum Genet. 2024 May;32(5):471-473. doi: 10.1038/s41431-024-01554-6. Epub 2024 Feb 13. Eur J Hum Genet. 2024. PMID: 38351291 Free PMC article. No abstract available.
Clinician-Driven Reanalysis of Exome Sequencing Data From Patients With Inherited Retinal Diseases.
Surl D, Won D, Lee ST, Lee CS, Lee J, Lim HT, Chung SA, Song WK, Kim M, Kim SS, Shin S, Choi JR, Sangermano R, Byeon SH, Bujakowska KM, Han J. Surl D, et al. JAMA Netw Open. 2024 May 1;7(5):e2414198. doi: 10.1001/jamanetworkopen.2024.14198. JAMA Netw Open. 2024. PMID: 38819824 Free PMC article.
Considerations for reporting variants in novel candidate genes identified during clinical genomic testing.
Chong JX, Berger SI, Baxter S, Smith E, Xiao C, Calame DG, Hawley MH, Rivera-Munoz EA, DiTroia S; Genomics Research to Elucidate the Genetics of Rare Diseases (GREGoR) Consortium; Bamshad MJ, Rehm HL. Chong JX, et al. bioRxiv [Preprint]. 2024 Jun 21:2024.02.05.579012. doi: 10.1101/2024.02.05.579012. bioRxiv. 2024. Update in: Genet Med. 2024 Oct;26(10):101199. doi: 10.1016/j.gim.2024.101199. PMID: 38370830 Free PMC article. Updated. Preprint.
Considerations for reporting variants in novel candidate genes identified during clinical genomic testing.
Chong JX, Berger SI, Baxter S, Smith E, Xiao C, Calame DG, Hawley MH, Rivera-Munoz EA, DiTroia S; Genomics Research to Elucidate the Genetics of Rare Diseases (GREGoR) Consortium; Bamshad MJ, Rehm HL. Chong JX, et al. Genet Med. 2024 Oct;26(10):101199. doi: 10.1016/j.gim.2024.101199. Epub 2024 Jun 26. Genet Med. 2024. PMID: 38944749
GREGoR: Accelerating Genomics for Rare Diseases.
Dawood M, Heavner B, Wheeler MM, Ungar RA, LoTempio J, Wiel L, Berger S, Bernstein JA, Chong JX, Délot EC, Eichler EE, Gibbs RA, Lupski JR, Shojaie A, Talkowski ME, Wagner AH, Wei CL, Wellington C, Wheeler MT; GREGoR Partner Members; Carvalho CMB, Gifford CA, May S, Miller DE, Rehm HL, Sedlazeck FJ, Vilain E, O'Donnell-Luria A, Posey JE, Chadwick LH, Bamshad MJ, Montgomery SB; Genomics Research to Elucidate the Genetics of Rare Diseases (GREGoR) Consortium. Dawood M, et al. ArXiv [Preprint]. 2024 Dec 18:arXiv:2412.14338v1. ArXiv. 2024. PMID: 39764392 Free PMC article. Preprint.

References

1. Maia N, Nabais Sá MJ, Melo-Pires M, de Brouwer APM, and Jorge P (2021). Intellectual disability genomics: current state, pitfalls and future challenges. BMC Genomics 22, 1–17. 10.1186/s12864-021-08227-4. - DOI - PMC - PubMed
1. Srivastava S, Love-Nichols JA, Dies KA, Ledbetter DH, Martin CL, Chung WK, Firth HV, Frazier T, Hansen RL, Prock L, et al. (2019). Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders. Genetics in Medicine. 10.1038/s41436-019-0554-6. - DOI - PMC - PubMed
1. Marshall CR, Chowdhury S, Taft RJ, Lebo MS, Buchan JG, Harrison SM, Rowsey R, Klee EW, Liu P, Worthey EA, et al. (2020). Best practices for the analytical validation of clinical whole-genome sequencing intended for the diagnosis of germline disease. NPJ Genom Med 5. 10.1038/s41525-020-00154-9. - DOI - PMC - PubMed
1. Ewans LJ, Schofield D, Shrestha R, Zhu Y, Gayevskiy V, Ying K, Walsh C, Lee E, Kirk EP, Colley A, et al. (2018). Whole-exome sequencing reanalysis at 12 months boosts diagnosis and is cost-effective when applied early in Mendelian disorders. Genetics in Medicine 20, 1564–1574. 10.1038/gim.2018.39. - DOI - PubMed
1. Schwarze K, Buchanan J, Taylor JC, and Wordsworth S (2018). Are whole-exome and whole-genome sequencing approaches cost-effective? A systematic review of the literature. Genetics in Medicine 20, 1122–1130. 10.1038/gim.2017.247. - DOI - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
- Elsevier Science
- PubMed Central
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Narrowing the diagnostic gap: Genomes, episignatures, long-read sequencing, and health economic analyses in an exome-negative intellectual disability cohort

Affiliations

Narrowing the diagnostic gap: Genomes, episignatures, long-read sequencing, and health economic analyses in an exome-negative intellectual disability cohort

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Miscellaneous

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Related information

Grants and funding

LinkOut - more resources

Full Text Sources

Miscellaneous