Development of Non-invasive Prenatal Test for Microdeletion and Other Genetic Syndromes Based on Cell Free DNA (Microdel Triad)

Development of Non-invasive Prenatal Test for Microdeletion/Duplication and Other Genetic Syndromes Based on Fetal DNA Isolated From Maternal Blood

The purpose of this study is to collect blood from families with a child who has been diagnosed with a chromosomal disorder including microdeletions in order to further develop a non-invasive prenatal screening test based on fetal DNA isolated from maternal blood.

Study Overview

• Status: Completed
• Conditions: Trisomy 21; Trisomy 18; Trisomy 13; Sex Chromosome Abnormalities; Microdeletion Syndromes

Detailed Description

The primary purpose of this study is to collect family triads from families affected by a genetic or microdeletion/duplication (MD/D) syndrome to further develop non-invasive prenatal testing based on fetal DNA isolated from maternal blood. To assist with the development of the test, we will need to collect blood samples from women whose child was diagnosed with a genetic or MD/D syndrome, a blood sample from that child as well as a blood sample from their confirmed unaffected siblings. Since the test is based on Natera's Parental Support™ technology, buccal or blood samples from the biological fathers will also be requested.

A recent abstract from a five year study on prenatal microarray testing revealed that 1.6% of women who present for routine prenatal indications have a positive microarray test. With the frequency of microdeletions and microduplications (MD/D) now known to be higher than previously thought, the field is likely to move toward offering invasive testing for microarray abnormalities to all pregnant women. Although non-invasive prenatal testing for aneuploidy is now clinically available, it has become clear that non-invasive prenatal testing for MD/D is equally important. However, access to these samples is made difficult as the standard of care for offering microarray analysis to all pregnant women will take time to come to fruition. We would like to develop this non-invasive as the standard of care so that less women will have to undergo invasive testing for the diagnosis of microarray abnormalities. Thus, there is an unmet need for the development of novel tests that would increase the scope of non-invasive prenatal screening.

• Study Type: Observational
• Enrollment (Actual): 216

Contacts and Locations

Study Locations

• United States
  • California
    • San Carlos, California, United States, 94070
      • Natera
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Families with a child affected by a chromosomal abnormality.

Description

Inclusion Criteria:

• Couples who have a child diagnosed with an autosomal chromosome abnormality (e.g. Down syndrome, Edwards syndrome, Patau syndrome).
• Couples who have a child diagnosed with a sex chromosome abnormality (e.g. Turner syndrome, Klinefelter syndrome, Triple X syndrome, 47, XYY).
• Couples who have a child diagnosed with a microdeletion/duplication syndrome (a positive microarray test).

Exclusion criteria:

• Not an English language or Spanish language speaker
• Genetics report is not available

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Mother child diads or triads; Families with child affected by genetic anomaly, microdeletion, microduplication, or chromosomal anomaly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Sensitivity and Specificity of the test to diagnose chromosomal microdeletions and aneuploidy in a fetus	4 years

Collaborators and Investigators

• Sponsor: Natera, Inc.
• Investigators: Principal Investigator: Kim Martin, MD, Natera, Inc.

Publications and helpful links

General Publications

• Wapner RJ, Babiarz JE, Levy B, Stosic M, Zimmermann B, Sigurjonsson S, Wayham N, Ryan A, Banjevic M, Lacroute P, Hu J, Hall MP, Demko Z, Siddiqui A, Rabinowitz M, Gross SJ, Hill M, Benn P. Expanding the scope of noninvasive prenatal testing: detection of fetal microdeletion syndromes. Am J Obstet Gynecol. 2015 Mar;212(3):332.e1-9. doi: 10.1016/j.ajog.2014.11.041. Epub 2014 Dec 2.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2012
• Primary Completion (ACTUAL): June 1, 2019
• Study Completion (ACTUAL): August 1, 2019

Study Registration Dates

• First Submitted: April 8, 2014
• First Submitted That Met QC Criteria: April 8, 2014
• First Posted (ESTIMATE): April 10, 2014

Study Record Updates

• Last Update Posted (ACTUAL): August 26, 2019
• Last Update Submitted That Met QC Criteria: August 21, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Down syndrome; 22q; 1p36; Angelman; DiGeorge; Turner syndrome; Patau syndrome; Edwards syndrome; Trisomy 21; Klinefelter syndrome; XXY; Prader Willi; Trisomy 13; Trisomy 18; Monosomy X; XXX; XYY; Cri du chat; Miller Dieker; Phelan McDermid; Wolf Hirschorn; Smith Magenis
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Intellectual Disability; Heart Defects, Congenital; Cardiovascular Abnormalities; Abnormalities, Multiple; Aneuploidy; Chromosome Duplication; Syndrome; Down Syndrome; Chromosome Disorders; Chromosome Aberrations; Trisomy; Trisomy 13 Syndrome; Trisomy 18 Syndrome; Sex Chromosome Aberrations
• Other Study ID Numbers: GSN014