Clinical Utility of Prenatal Whole Exome Sequencing

NCT03482141 | Completed Results FDA Device

• 1 other identifier: 17-22420
• Study Type: interventional
• Target: 316
• Locations: 1 country
• Sites: 1

Brief Summary

The investigator aims to examine the clinical utility of WES, including assessment of a variety of health-related and reproductive outcomes in undiagnosed prenatal cases.

Conditions

Structural Anomalies; Cardiac Anomalies; Central Nervous System Anomalies; Thorax Anomalies; Genito-urinary Anomalies; Gastrointestinal Anomalies; Skeletal Anomalies; Multiple Anomalies

Outcome Measures

Primary Outcomes (1)

• Diagnostic Yield of Prenatal Exome in Patients With Fetal Structural Anomalies

  Number of prenatal patients (pregnancies with a structural anomaly) who got a positive exome result among those who had the exome test. Positive exome result is defined as identification of definitive or probable positive variants which explain prenatal phenotype.

  Follow-up was done 6 months after return of exome results.

Study Arms (1)

Whole Exome Sequencing

OTHER

Whole exome sequencing (WES) will take place for prenatal patients (pregnancies with fetal structural defects). All patients will get exome sequencing and will follow the same procedures.

Device: Whole Exome Sequencing (WES)

Interventions

Whole Exome Sequencing (WES) DEVICE

The Investigators will enroll pregnant women with fetal anomalies detected by ultrasound. Patients will be approached by a maternal-fetal specialist, who has counseled the patient regarding the fetal anomaly that has been detected. Written informed consent will be obtained by the study prenatal genetic counselor. Many patients will have undergone prenatal diagnostic testing in an outside laboratory; in such cases, cells or extracted DNA from the original fetal sample will be used for the purpose of this study. The consent process for prenatal WES will include pre-test counseling and the option of choosing whether or not to receive uncertain results and secondary findings. After conducting whole exome sequencing, the findings will be shared with the parent(s). Routine medical care will be provided to patients. The research will study the effectiveness of sequencing as a tool for providing genetic information to parents when a prenatal study reveals a fetus with a structural anomaly.

Whole Exome Sequencing

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Women carrying a pregnancy with an ultrasound diagnosis of a major structural anomaly (or multiple anomalies) in a major organ system (cardiac, central nervous system, thorax, genito-urinary, gastrointestinal/ventral wall, skeletal and or multiple anomalies )
• Clinical concern for a potential underlying genetic condition
• Completed or plan to complete chorionic villus sampling or amniocentesis with chromosome analysis or microarray
• Available maternal sample

You may not qualify if:

• Prior WES performed for a clinical or research indication
• Lack of phenotypic indication of a likely underlying genetic etiology
• Mother unwilling or unable to provide a specimen

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

University of California San Francisco

San Francisco, California, 94143, United States

Location

Related Publications (6)

• Yang Y, Muzny DM, Reid JG, Bainbridge MN, Willis A, Ward PA, Braxton A, Beuten J, Xia F, Niu Z, Hardison M, Person R, Bekheirnia MR, Leduc MS, Kirby A, Pham P, Scull J, Wang M, Ding Y, Plon SE, Lupski JR, Beaudet AL, Gibbs RA, Eng CM. Clinical whole-exome sequencing for the diagnosis of mendelian disorders. N Engl J Med. 2013 Oct 17;369(16):1502-11. doi: 10.1056/NEJMoa1306555. Epub 2013 Oct 2.

  PMID: 24088041 BACKGROUND

• Norton ME, Rink BD. Changing indications for invasive testing in an era of improved screening. Semin Perinatol. 2016 Feb;40(1):56-66. doi: 10.1053/j.semperi.2015.11.008. Epub 2015 Dec 24.

  PMID: 26725145 BACKGROUND

• Cowan RS. Aspects of the history of prenatal diagnosis. Fetal Diagn Ther. 1993 Apr;8(Suppl. 1):10-7. doi: 10.1159/000263869.

  PMID: 11653011 BACKGROUND

• Chervenak FA, McCullough LB. Ethical issues in perinatal genetics. Semin Fetal Neonatal Med. 2011 Apr;16(2):70-3. doi: 10.1016/j.siny.2010.10.004. Epub 2010 Nov 3.

  PMID: 21051301 BACKGROUND

• Donley G, Hull SC, Berkman BE. Prenatal whole genome sequencing: just because we can, should we? Hastings Cent Rep. 2012 Jul-Aug;42(4):28-40. doi: 10.1002/hast.50. Epub 2012 Jun 20.

  PMID: 22777977 BACKGROUND

• Rego S, Hoban H, Outram S, Zamora AN, Chen F, Sahin-Hodoglugil N, Anguiano B, Norstad M, Yip T, Lianoglou B, Sparks TN, Norton ME, Koenig BA, Slavotinek AM, Ackerman SL. Perspectives and preferences regarding genomic secondary findings in underrepresented prenatal and pediatric populations: A mixed-methods approach. Genet Med. 2022 Jun;24(6):1206-1216. doi: 10.1016/j.gim.2022.02.004. Epub 2022 Apr 8.

  PMID: 35396980 DERIVED

MeSH Terms

Conditions

Heart Defects, Congenital; Abnormalities, Multiple

Interventions

Exome Sequencing

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Whole Genome Sequencing; Sequence Analysis, DNA; Sequence Analysis; Genetic Techniques; Investigative Techniques

Results Point of Contact

• Title: Mary Norton
• Organization: University of California, San Francisco

mary.norton@ucsf.edu

(415) 467 4080

Study Officials

• Mary Norton, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2018
• First Posted: March 29, 2018
• Study Start: August 1, 2017
• Primary Completion: May 13, 2022
• Study Completion: May 13, 2022
• Last Updated: April 14, 2023
• Results First Posted: April 14, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)