Whole Exome Sequencing and Whole Genome Sequencing for Nonimmune Fetal/Neonatal Hydrops

Conditions

• Genetic Disorders
• Nonimmune Fetal Hydrops
• Nonimmune Hydrops in Neonate

Eligibility Criteria

Sex

ALL

Age

16 Years - 55 Years

Healthy Volunteers

Not accepted

Interventions

• Whole Exome Sequencing — DIAGNOSTIC_TEST
  Whole exome sequencing (WES) provides more detailed information through greater resolution, identifying single base-pair changes and small insertions and deletions. WES performs sequencing on the protein-coding exons, which are contained in 1-2% of the genome but make up over 85% of all known pathogenic mutations.
• Whole Genome Sequencing — DIAGNOSTIC_TEST
  Whole Genome Sequencing (WGS) has emerged in recent years as a diagnostic tool that sequences the entire genome and can pick up insertions or deletion of bases, structural variants and intronic single nucleotide variations.

Study Details

Brief Summary: Nonimmune hydrops fetalis (NIHF) is a potentially fatal condition characterized by abnormal fluid accumulation in two or more fetal compartments. Numerous etiologies may lead to NIHF, and the underlying cause often remains unclear (1). The current standard of genetic diagnostic testing includes a fetal karyotype and chromosomal microarray (CMA), with an option to pursue single gene testing on amniocytes collected by amniocentesis (2). A large subgroup of the NIHF causes includes single gene disorders that are not diagnosed with the standard genetic workup for hydrops. Currently, nearly 1 in 5 cases of NIHF is defined as idiopathic, meaning there is no identified etiology (2). The investigators believe this is because the causes of NIHF are not completely investigated, specifically single gene disorders. Our research study aims to increase the diagnostic yield by performing whole exome sequencing (WES) and whole genome sequencing (WGS) on prenatal and neonatal NIHF cases when standard genetic testing is negative, identifying known and new genes, thus providing vital information to families regarding the specific diagnosis and risk to future pregnancies. The investigators plan to perform WES as the initial diagnostic test. If WES is negative, then the investigators will proceed to perform WGS.

Key Dates

Start date

Jan 15, 2019

Status verified

Nov 2024

Primary completion

Jun 30, 2028

Completion

Dec 31, 2028

Study Design

Enrollment

55 participants (estimated)

Arms

• Arm: Fetuses
  DNA obtained from amniotic fluid samples
• Arm: Neonates
  DNA obtained from neonatal blood samples

Primary Outcome Measure

Identify known single gene disorders that would not be detected by microarray as a cause of nonimmune fetal hydrops by performing whole exome sequencing (WES) [ Time Frame: 5 years ]

Central Contacts

• Huda B Al-Kouatly, MD
  215-955-9200
  [email protected]
• Stephanie M Rice, MS
  [email protected]

Locations (1)

Find similar trials in Philadelphia, PA

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