Implications of Maternal 45,X Mosaicism as a Secondary Genomic Finding Following Cell-Free DNA Sequencing During Pregnancy: A Deep Phenotype Study

Hypertensive Disease Clinical Trial

Official title: Implications of Maternal 45,X Mosaicism As A Secondary Genomic Finding Following Cell-free DNA Sequencing During Pregnancy: A Deep Phenotype Study

Status Not yet recruiting

Clinical Trial Summary

Background:

Mosaicism is a condition in which cells within the same person have a different genetic makeup. Sometimes, a type of mosaicism called 45,X may not be discovered in a woman until she undergoes routine tests during pregnancy. Little is known about how 45,X mosaicism may affect a person s long-term health.

Objective:

This natural history study will look for health risks in people with 45,X mosaicism.

Eligibility:

People aged 18 to 99 years who during pregnancy were found to have 45,X mosaicism. Healthy volunteers are also needed.

Design:

Participants will stay in the clinic for 2 days. They will have many tests:

A physical exam, including measurements of the body.

A gynecological exam, including genital measurements. Photos may be taken, with consent.

Blood tests, with blood drawn over an 8-week period. An oral glucose test for diabetes may also be done.

Tests of heart function. Participants will have small stickers attached to wires place on their chest, arms, and legs.

Hearing tests.

Ultrasound exams, which use echoing sound waves to create images of organs such as the heart and kidneys.

Imaging scans including x-rays, MRI, and DXA. The DXA uses x-rays to measure bone density and body fat. Other types of scans will capture images of the liver.

Participants will complete 4 surveys with questions about their sexual function, anxiety, depression, and health.

Participants may remain in the study for 20 years. For 5 years, they will have a yearly follow-up by phone or email. They may have follow-up visits at the clinic every 5 years.

Clinical Trial Description

Study Description:

This is a deep phenotype study of women who are determined to have 45,X mosaicism as a secondary genomic finding following cfDNA sequencing during pregnancy.

Objectives:

• To define and describe a comprehensive phenotype of women with confirmed 45,X mosaicism initially found by cfDNA including cardiovascular, skeletal, metabolic, reproductive, audiometric, immunologic, and psychological functions.

• To compare the comprehensive phenotype of women with confirmed 45,X mosaicism with a control population (a. age and BMI-matched female controls without 45, X mosaicism at the initial visit and b. NHANES age-and BMI-matched female data for the applicable year.)

• To explore changes in phenotype for both 45,X mosaicism and control groups with somatic loss of X chromosome over time.

Endpoints:

Primary Endpoint: (i) Hypertension (as defined in 2017 by the American College of Cardiology/American Heart Association (ACC/AHA)

Secondary Endpoints:

• Cardiovascular:

• Cardiac/coronary atherosclerosis

• Cardiac function, valve assessment, aortic anatomy, endothelial function

• Skeletal:

• Height

• Areal bone mineral density (aBMD) as per DXA

• Bone turnover markers

• Bone microarchitecture using trabecular bone score as per DXA

• Occult fractures using vertebral fracture assessment as per DXA

• Skeletal morphology for assessment of scoliosis

• Metabolic:

• Body fat distribution as per DXA

• Anthropometrics; Body weight; Waist to hip ratio

• Diabetes Mellitus

• Thyroid disorders

• Dyslipidemia

• Assessment of liver for fatty disease and fibrosis as per abdominal MRE/MRS

• Gynecologic and urologic:

• Markers of gonadal function and ovarian reserve

• Primary ovarian insufficiency, Infertility, Early menopause as per participant history

• Sexual function (as assessed by scores of the Female Sexual Function Index (FSFI) and the PROMIS(Registered Trademark) Sexual Function and Satisfaction Measures Version 2.0)

• Ovarian and uterine imaging as per pelvic ultrasound.

• Renal imaging as per renal ultrasound

• Obstetric:

--Complications and outcomes of pregnancy as per participant history

• Audiometric:

--Assessment of hearing loss

• Immunologic

• Immune biomarkers

• Celiac disease

• Psychological:

• PROMIS(Registered Trademark) Item Bank v1.0 - Emotional Distress - Anxiety - Short Form 8a

• PROMIS(Registered Trademark) Item Bank v.1.0 - Emotional Distress - Depression - Short Form 8b

• PROMIS(Registered Trademark) Scale v.1.2 - Global Health

Exploratory endpoints: Changes in phenotype (as outlined above) for both 45,X mosaicism and control groups with somatic loss of X chromosome over time. ;

Related Conditions & MeSH terms

• Hypertension
• Hypertensive Disease

• NCT number: NCT05548881
• Study type: Observational
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Harveen Kaur
• Phone: (301) 451-1777
• Email: harveen.kaur@nih.gov
• Status: Not yet recruiting
• Start date: June 26, 2024
• Completion date: December 31, 2042