Genetic DiseasesrWGSNCT03385876

Rapid Whole Genome Sequencing Study

A study testing Genomic sequencing and molecular diagnostic results, if any in people with Genetic Diseases and Genetic Syndrome, run by Rady Pediatric Genomics & Systems Medicine Institute at 1 site in United States.

Enrolling by invitation

Enrolling by invitation. The study team selects and invites participants, usually from an existing group of patients.

Sites and contacts

Official record

Search all trials

Trial summary

Who is it for?: Any ageHealthy volunteers can take part
Conditions the study is for: Genetic Diseases, Genetic Syndrome
What is being tested?: Genomic sequencing and molecular diagnostic results, if any
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 100,000 participants
Where: 1 siteUnited States
Study dates: 29 Aug 2017to 31 Dec 2050
Phase: Interventional
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Any age
All sexes
Healthy volunteers accepted
Child, Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

United States1 site

Rady Children's Institute for Genomic Medicine
San Diego, California, 92123

Other trials in United States

About this study

Official title: Rapid Whole Genome Sequencing (rWGS): Rapid Genomic Sequencing for Acutely Ill Patients and the Collection, Storage, Analysis, and Distribution of Biological Samples, Genomic and Clinical Data

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.

Read the detailed description

Rapid Whole Genome Sequencing (rWGS) is a new technology that is able to deliver symptom-driven diagnoses of childhood-onset genetic diseases in as little as 26 hours. Investigators at RCIGM have shown that rWGS has higher diagnostic rates than traditional molecular testing in acutely ill infants suspected of a genetic diagnosis, with diagnostic rates up to 57%. Similarly, in the infant population, RCIGM researchers have shown that these diagnoses are useful in directing clinical care, with up to 70% of infants who receive a diagnosis having a subsequent change in management. In some cases, a timely diagnosis results in treatments that are lifesaving. RCIGM investigators have shown that up to 25% of infants who receive a diagnosis have a subsequent change in management that prevents morbidity. More data is needed to determine whether these results are found at other institutions, among other ethnic and racial groups, and in larger numbers of patients. More data is needed to examine the acute and long-term clinical utility of such testing, both in newborns and older children, as well as to determine the cost-effectiveness of this testing for other institutions. As such, this study will be a collaboration of multiple sites to share data and experiences of rWGS with the scientific community as well as hospital administrations, insurance companies and other key stakeholders who may be interested in promoting rWGS as a first-line clinical test in the future.

The study will provide clinical laboratory-confirmed results related to the affected patient's symptoms, including optional incidental findings unless subjects opt-out for these additional results, to allow for these research findings to be used in clinical care. Furthermore, this study will aggregate data regarding standard clinical genetic testing from multiple sites as well as cost measures to not only identify differences in diagnostic rates, diagnostic accuracy, and times to diagnoses, but to determine the cost-effectiveness of this testing and subsequent changes in care management. Clinical utility will be defined as changes in care that follow directly from results of genetic testing (both positive and negative), including standard clinical tests and rWGS. This data will be used to further examine the analytic, diagnostic, and clinical utility and cost-effectiveness of this testing.

rWGS methods continue to improve, and pediatric genomic medicine is a very new field of medical practice. This study will also inform investigators regarding best practices, both in terms of traditional medical outcomes and patient-centered outcomes. Consequently, this study will also act as a biorepository for samples and data as the ability to share genomic and phenotypic data amongst researchers is critical to progressing our understanding of the nascent field of pediatric genomic medicine.

Specific Aims:

To collect biological samples and associated clinical data from acutely ill pediatric patients who may have a genetic disease and their family members (Phenome).
To create, analyze and store genomic data from the biological samples. Genomic data will include genomic (gDNA) sequences, RNA sequences, and/or other related 'omic data (including, but not limited to, pharmacogenomics, transcriptomics, and epigenomics). Genomic data from rWGS will include single nucleotide calls (SNVs), structural variants such as copy number testing, genomic rearrangements, gene expression , the "whole transcriptome" or more limited DNA sequencing panels of specific genes or of all exons of genes (the "Exome").
To evaluate the diagnosis rate of genetic diseases by rWGS in an acutely ill population enrolling from multiple sites with comparisons to standard clinical genetic testing.
To assess the clinical utility of rapid genetic diagnoses in the care and management of patients.
To examine the health economics and cost-effectiveness of this rapid testing across many sites.
To investigate and improve genomics technologies and software to enhance understanding and testing abilities related to childhood diseases and potential treatment responses.
To make specimens and data available for qualified researchers and collaborators to further the understanding of rare childhood diseases and treatment responses.
To collect and correlate genomic data from a wide variety of populations and clinical presentations.
To provide sample and data collections with uniform consent, methods of acquisition, storage for genome-based research studies with subsequent IRB approvals.
To analyze and report clinically-confirmed genomic diagnoses and treatment guidance through use of new research technologies.
To identify and study novel gene and disease processes.

Conditions: Genetic Diseases, Genetic Syndrome
Being tested: Genomic sequencing and molecular diagnostic results, if any
Keywords: Rady Children's, Pediatric, Genomic, Precision Medicine, Biorepository
Medical subject headings: Genetic Diseases, Inborn

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Genomic sequencing and molecular diagnostic results, if anyGenetic
Also called Pediatric Genetic Biorepository, Pediatric Precision Medicine
Samples will be stored in the pediatric genomic biorepository. A subset of samples will undergo genetic/genomic analysis.

Study groups in NCT03385876
Study group	Role	What they receive
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. Receives: Genetic: Genomic sequencing and molecular diagnostic results, if any

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Yearly through study completion estimated to be 40 years.

Secondary outcomes (5)

Proportion of children receiving molecular diagnoses
Utilize cutting edge technologies to improve both diagnostic rates and time to diagnosis for rare genetic diseases. Symptom driven return of results and analysis of clinical utility.
Measured: Through study completion estimated to be 40 years.
Time taken to receive molecular diagnosis
Measured: 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
Measured: Through study completion estimated to be 40 years.
Subject's main provider's perceived clinical utility of genomic sequencing
Perceived utility/benefit of sequencing based on "Clinician Assessment" scale completed by patient's providers.
Measured: Within one month of the return of results.
Comparing diagnostic rates between singleton and trio analysis
Marginal increase in diagnostic yield above singleton analysis based on the number of clinically confirmed diagnoses posted in medical record following singleton and trio levels of analysis in cases when both biological parents are available.
Measured: Within 30 days of enrollment.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

29 Aug 201731 Dec 2050

First posted29 Dec 2017
Study start29 Aug 2017
Primary completion31 Dec 2050 (estimated)
Study completion31 Dec 2050 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (13)Papers the sponsor has linked to this study.
Other trials for Genetic DiseasesStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Diagnosis
Allocation: Not applicable
Intervention model: Single group
Model description: Assignment
Masking: None (open label)
Enrolment: 100,000 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03385876
Sponsor's protocol ID: rWGS Protocol #20171726
Acronym: rWGS
Status last verified: Dec 2021
First submitted: 13 Dec 2017
Last updated: 23 Dec 2021
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 34077649
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.
PubMed 34076366
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.
PubMed 34040193
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.
PubMed 33888711
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.
PubMed 33855675
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.
PubMed 33046443
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.
PubMed 32620939
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.
PubMed 33749980
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.
PubMed 31624069
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.
PubMed 31788263
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.
PubMed 31019026
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.
PubMed 32014857
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.
PubMed 30755602

Interested in taking part?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 23 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Rapid Whole Genome Sequencing (rWGS): Rapid Genomic Sequencing for Acutely Ill Patients and the Collection, Storage, Analysis, and Distribution of Biological Samples, Genomic and Clinical Data
ClinicalTrials.gov ID: NCT03385876
Acronym / sponsor ID: rWGS / rWGS Protocol #20171726
Conditions: Genetic Diseases, Genetic Syndrome
Keywords: Rady Children's, Pediatric, Genomic, Precision Medicine, Biorepository
Study type: Interventional
Recruitment status: Enrolling by invitation
Enrolment: 100,000 participants (estimated)
Lead sponsor: Rady Pediatric Genomics & Systems Medicine InstituteUniversity, hospital or other
Study start: 29 Aug 2017 (actual)
Primary completion: 31 Dec 2050 (estimated)
Study completion: 31 Dec 2050 (estimated)
First posted: 29 Dec 2017 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Specific Aims:

To collect biological samples and associated clinical data from acutely ill pediatric patients who may have a genetic disease and their family members (Phenome).
To create, analyze and store genomic data from the biological samples. Genomic data will include genomic (gDNA) sequences, RNA sequences, and/or other related 'omic data (including, but not limited to, pharmacogenomics, transcriptomics, and epigenomics). Genomic data from rWGS will include single nucleotide calls (SNVs), structural variants such as copy number testing, genomic rearrangements, gene expression , the "whole transcriptome" or more limited DNA sequencing panels of specific genes or of all exons of genes (the "Exome").
To evaluate the diagnosis rate of genetic diseases by rWGS in an acutely ill population enrolling from multiple sites with comparisons to standard clinical genetic testing.
To assess the clinical utility of rapid genetic diagnoses in the care and management of patients.
To examine the health economics and cost-effectiveness of this rapid testing across many sites.
To investigate and improve genomics technologies and software to enhance understanding and testing abilities related to childhood diseases and potential treatment responses.
To make specimens and data available for qualified researchers and collaborators to further the understanding of rare childhood diseases and treatment responses.
To collect and correlate genomic data from a wide variety of populations and clinical presentations.
To provide sample and data collections with uniform consent, methods of acquisition, storage for genome-based research studies with subsequent IRB approvals.
To analyze and report clinically-confirmed genomic diagnoses and treatment guidance through use of new research technologies.
To identify and study novel gene and disease processes.

Study design

Primary purpose: Diagnosis
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: Assignment

Arm	Type	Receives
Enrollees	Experimental	Genetic: Genomic sequencing and molecular diagnostic results, if anyEnrollment 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.

Who may qualify

Sex: All
Healthy volunteers: Accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (1 listed)

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.

Key exclusion criteria (2 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Genomic sequencing and molecular diagnostic results, if anyAlso: Pediatric Genetic Biorepository, Pediatric Precision MedicineSamples will be stored in the pediatric genomic biorepository. A subset of samples will undergo genetic/genomic analysis.	Genetic	Enrollees

Primary outcome

Number of samples enrolled per year
Time frame: Yearly through study completion estimated to be 40 years.
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.

5 secondary outcomes

Proportion of children receiving molecular diagnoses
Time frame: Through study completion estimated to be 40 years.
Time taken to receive molecular diagnosis
Time frame: 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
Time frame: Through study completion estimated to be 40 years.
Subject's main provider's perceived clinical utility of genomic sequencing
Time frame: Within one month of the return of results.
Comparing diagnostic rates between singleton and trio analysis
Time frame: Within 30 days of enrollment.

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Dec 2021.
Results publication: PubMed 34077649Owen 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.
Results publication: PubMed 34076366Friedman 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.
Results publication: PubMed 34040193Rossignol 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.
Results publication: PubMed 33888711Sweeney 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.
Results publication: PubMed 33855675Kuehn 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.
Results publication: PubMed 33046443Rusert 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.
Results publication: PubMed 32620939Ramchandar 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.
Results publication: PubMed 33749980Chandrasekar 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.
Results publication: PubMed 31624069Tokita 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.
Results publication: PubMed 31788263Kadakia 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.
Results publication: PubMed 31019026Clark 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.
Results publication: PubMed 32014857Kingsmore 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

David Dimmock, MD principal investigator

Rady Pediatric Genomics & Systems Medicine Institute

Stephen Kingsmore study director

Rady Pediatric Genomics & Systems Medicine Institute

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: enrolling by invitation, as of the sponsor's last update on 23 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of samples enrolled per year (time frame: Yearly through study completion estimated to be 40 years.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03385876, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Dec 2021.