Rapid Whole Genome Sequencing Study

NCT03385876 | Enrolling By Invitation

• 1 other identifier: rWGS Protocol #20171726
• Study Type: interventional
• Target: 100,000
• Locations: 1 country
• Sites: 1

Brief Summary

Rapid Whole Genome Sequencing (rWGS) has proven to provide much faster diagnoses than traditional clinical testing, including clinical Whole Exome Sequencing (WES) and standard Whole Genome Sequencing (WGS). This collaborative study seeks to provide rWGS as a research test to additional pediatric hospitals nationwide to assist in the rapid diagnosis of acutely ill children suspected of a genetic condition. The study will examine diagnosis rates, changes in clinical care as a result of a genetic diagnosis, and health economics including potential cost-effectiveness of rWGS. This study will also serve as a biorepository for future research on samples and data generated from genomic sequencing.

Conditions

Genetic Diseases; Genetic Syndrome

Keywords

Rady Children's; Pediatric; Genomic; Precision Medicine; Biorepository

Outcome Measures

Primary Outcomes (1)

• Number of samples enrolled per year

  Establishment of a biorepository for genomic/precision medicine use in pediatric population. This will make samples available to study rare genetic disorders, screening methods, diagnostic methods, other "omics," and bench research for possible treatments.

  Yearly through study completion estimated to be 40 years.

Secondary Outcomes (5)

• Proportion of children receiving molecular diagnoses

  Through study completion estimated to be 40 years.

• Time taken to receive molecular diagnosis

  From date of enrollment until the date of documented clinical laboratory diagnosis or date of death from any cause, whichever came first, assessed up to 10 years.

• Proportion of children in which human phenotype ontology (HPO) terms accurately predict molecular diagnosis

  Through study completion estimated to be 40 years.

• Subject's main provider's perceived clinical utility of genomic sequencing

  Within one month of the return of results.

• Comparing diagnostic rates between singleton and trio analysis

  Within 30 days of enrollment.

Study Arms (1)

Enrollees

EXPERIMENTAL

Enrollment of healthy and affected subjects to collect samples and data for a pediatric genomic biorepository. Data includes genomic sequencing and resultant molecular diagnostic results, if any.

Genetic: Genomic sequencing and molecular diagnostic results, if any

Interventions

Genomic sequencing and molecular diagnostic results, if any GENETIC

Samples will be stored in the pediatric genomic biorepository. A subset of samples will undergo genetic/genomic analysis.

Also known as: Pediatric Genetic Biorepository, Pediatric Precision Medicine

Enrollees

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• The Repository will be comprised of samples from symptomatic patients, individuals reported to be their (symptomatic or asymptomatic) biologic family members, and control individuals. In this context a "symptomatic patient" is characterized as a patient whose treating physician has identified phenotypic features and/or signs of illness potentially attributable to a genetic disorder (also referred to as "Affected" or "Proband"). There will be no age, gender, race, or health restrictions for this Biorepository Study. However, since this study will be performed at children's hospitals and since genetic disorders are more likely to be present in children less than 4 months of age these cases will likely be preferentially enrolled. Preference will also be given to those who are acutely ill, suspected of a genetic condition, and for whom a diagnosis may result in change of clinical management.

You may not qualify if:

• Participants will be excluded if they are unwilling to consent to research.
• A patient may be determined ineligible if there is a prior diagnosis that explains their clinical presentation, if other traditional clinical genetic testing is more appropriate at the time of referral, if the clinical presentation is insufficient at the time of referral to suggest a genetic etiology, if the parents are unable or unwilling to provide permission for participation, if child protective services is involved in the case unless the child's life is in immediate danger and research holds out a prospect of direct benefit that is important to the health or well-being of the child and is available only in the context of the research in which case permission will be obtained from the party legally responsible for medical decisions.

Sponsors & Collaborators

• Rady Pediatric Genomics & Systems Medicine Institute: lead

Study Sites (1)

Rady Children's Institute for Genomic Medicine

San Diego, California, 92123, United States

Location

Related Publications (13)

• Owen MJ, Niemi AK, Dimmock DP, Speziale M, Nespeca M, Chau KK, Van Der Kraan L, Wright MS, Hansen C, Veeraraghavan N, Ding Y, Lenberg J, Chowdhury S, Hobbs CA, Batalov S, Zhu Z, Nahas SA, Gilmer S, Knight G, Lefebvre S, Reynders J, Defay T, Weir J, Thomson VS, Fraser L, Lajoie BR, McPhail TK, Mehtalia SS, Kunard CM, Hall KP, Kingsmore SF. Rapid Sequencing-Based Diagnosis of Thiamine Metabolism Dysfunction Syndrome. N Engl J Med. 2021 Jun 3;384(22):2159-2161. doi: 10.1056/NEJMc2100365. No abstract available.

  PMID: 34077649 RESULT

• Friedman J, Bird LM, Haas R, Robbins SL, Nahas SA, Dimmock DP, Yousefzadeh MJ, Witt MA, Niedernhofer LJ, Chowdhury S. Ending a diagnostic odyssey: Moving from exome to genome to identify cockayne syndrome. Mol Genet Genomic Med. 2021 Jul;9(7):e1623. doi: 10.1002/mgg3.1623. Epub 2021 Jun 2.

  PMID: 34076366 RESULT

• Rossignol F, Duarte Moreno MS, Benoist JF, Boehm M, Bourrat E, Cano A, Chabrol B, Cosson C, Diaz JLD, D'Harlingue A, Dimmock D, Freeman AF, Garcia MT, Garganta C, Goerge T, Halbach SS, de Laffolie J, Lam CT, Martin L, Martins E, Meinhardt A, Melki I, Ombrello AK, Perez N, Quelhas D, Scott A, Slavotinek AM, Soares AR, Stein SL, Sussmuth K, Thies J, Ferreira CR, Schiff M. Quantitative analysis of the natural history of prolidase deficiency: description of 17 families and systematic review of published cases. Genet Med. 2021 Sep;23(9):1604-1615. doi: 10.1038/s41436-021-01200-2. Epub 2021 May 26.

  PMID: 34040193 RESULT

• Sweeney NM, Nahas SA, Chowdhury S, Batalov S, Clark M, Caylor S, Cakici J, Nigro JJ, Ding Y, Veeraraghavan N, Hobbs C, Dimmock D, Kingsmore SF. Rapid whole genome sequencing impacts care and resource utilization in infants with congenital heart disease. NPJ Genom Med. 2021 Apr 22;6(1):29. doi: 10.1038/s41525-021-00192-x.

  PMID: 33888711 RESULT

• Kuehn HS, Gloude NJ, Dimmock D, Tokita M, Wright M, Rosenzweig SD, Collins C. Abnormal SCID Newborn Screening and Spontaneous Recovery Associated with a Novel Haploinsufficiency IKZF1 Mutation. J Clin Immunol. 2021 Aug;41(6):1241-1249. doi: 10.1007/s10875-021-01035-1. Epub 2021 Apr 14.

  PMID: 33855675 RESULT

• Rusert JM, Juarez EF, Brabetz S, Jensen J, Garancher A, Chau LQ, Tacheva-Grigorova SK, Wahab S, Udaka YT, Finlay D, Seker-Cin H, Reardon B, Grobner S, Serrano J, Ecker J, Qi L, Kogiso M, Du Y, Baxter PA, Henderson JJ, Berens ME, Vuori K, Milde T, Cho YJ, Li XN, Olson JM, Reyes I, Snuderl M, Wong TC, Dimmock DP, Nahas SA, Malicki D, Crawford JR, Levy ML, Van Allen EM, Pfister SM, Tamayo P, Kool M, Mesirov JP, Wechsler-Reya RJ. Functional Precision Medicine Identifies New Therapeutic Candidates for Medulloblastoma. Cancer Res. 2020 Dec 1;80(23):5393-5407. doi: 10.1158/0008-5472.CAN-20-1655. Epub 2020 Oct 12.

  PMID: 33046443 RESULT

• Ramchandar N, Ding Y, Farnaes L, Dimmock D, Hobbs C, Kingsmore SF, Bainbridge M. Diagnosis of cytomegalovirus infection from clinical whole genome sequencing. Sci Rep. 2020 Jul 3;10(1):11020. doi: 10.1038/s41598-020-67656-5.

  PMID: 32620939 RESULT

• Chandrasekar I, Tourney A, Loo K, Carmichael J, James K, Ellsworth KA, Dimmock D, Joseph M. Hemimegalencephaly and intractable seizures associated with the NPRL3 gene variant in a newborn: A case report. Am J Med Genet A. 2021 Jul;185(7):2126-2130. doi: 10.1002/ajmg.a.62185. Epub 2021 Mar 22.

  PMID: 33749980 RESULT

• Tokita MJ, Nahas S, Briggs B, Malicki DM, Mesirov JP, Reyes IAC, Farnaes L, Levy ML, Kingsmore SF, Dimmock D, Crawford JR, Wechsler-Reya RJ. Biallelic loss of GNAS in a patient with pediatric medulloblastoma. Cold Spring Harb Mol Case Stud. 2019 Oct 23;5(5):a004572. doi: 10.1101/mcs.a004572. Print 2019 Oct.

  PMID: 31624069 RESULT

• Kadakia S, Farnaes L, Dimmock D, Chowdhury S, Ding Y, Anderson EJ, Kingsmore S, Newfield RS. Diagnosis and treatment of a boy with IPEX syndrome presenting with diabetes in early infancy. Clin Case Rep. 2019 Sep 27;7(11):2123-2127. doi: 10.1002/ccr3.2438. eCollection 2019 Nov.

  PMID: 31788263 RESULT

• Clark MM, Hildreth A, Batalov S, Ding Y, Chowdhury S, Watkins K, Ellsworth K, Camp B, Kint CI, Yacoubian C, Farnaes L, Bainbridge MN, Beebe C, Braun JJA, Bray M, Carroll J, Cakici JA, Caylor SA, Clarke C, Creed MP, Friedman J, Frith A, Gain R, Gaughran M, George S, Gilmer S, Gleeson J, Gore J, Grunenwald H, Hovey RL, Janes ML, Lin K, McDonagh PD, McBride K, Mulrooney P, Nahas S, Oh D, Oriol A, Puckett L, Rady Z, Reese MG, Ryu J, Salz L, Sanford E, Stewart L, Sweeney N, Tokita M, Van Der Kraan L, White S, Wigby K, Williams B, Wong T, Wright MS, Yamada C, Schols P, Reynders J, Hall K, Dimmock D, Veeraraghavan N, Defay T, Kingsmore SF. Diagnosis of genetic diseases in seriously ill children by rapid whole-genome sequencing and automated phenotyping and interpretation. Sci Transl Med. 2019 Apr 24;11(489):eaat6177. doi: 10.1126/scitranslmed.aat6177.

  PMID: 31019026 RESULT

• Kingsmore SF, Ramchandar N, James K, Niemi AK, Feigenbaum A, Ding Y, Benson W, Hobbs C, Nahas S, Chowdhury S, Dimmock D. Mortality in a neonate with molybdenum cofactor deficiency illustrates the need for a comprehensive rapid precision medicine system. Cold Spring Harb Mol Case Stud. 2020 Feb 3;6(1):a004705. doi: 10.1101/mcs.a004705. Print 2020 Feb.

  PMID: 32014857 RESULT

• Friedman J, Smith DE, Issa MY, Stanley V, Wang R, Mendes MI, Wright MS, Wigby K, Hildreth A, Crawford JR, Koehler AE, Chowdhury S, Nahas S, Zhai L, Xu Z, Lo WS, James KN, Musaev D, Accogli A, Guerrero K, Tran LT, Omar TEI, Ben-Omran T, Dimmock D, Kingsmore SF, Salomons GS, Zaki MS, Bernard G, Gleeson JG. Biallelic mutations in valyl-tRNA synthetase gene VARS are associated with a progressive neurodevelopmental epileptic encephalopathy. Nat Commun. 2019 Feb 12;10(1):707. doi: 10.1038/s41467-018-07067-3.

  PMID: 30755602 RESULT

MeSH Terms

Conditions

Genetic Diseases, Inborn

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• David Dimmock, MD

  Rady Pediatric Genomics & Systems Medicine Institute

  PRINCIPAL INVESTIGATOR

• Stephen Kingsmore

  Rady Pediatric Genomics & Systems Medicine Institute

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director

Model Details: Assignment

Study Record Dates

• First Submitted: December 13, 2017
• First Posted: December 29, 2017
• Study Start: August 29, 2017
• Primary Completion (Estimated): December 31, 2050
• Study Completion (Estimated): December 31, 2050
• Last Updated: December 23, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)