Whole Exome Sequencing and Whole Genome Sequencing for Nonimmune Fetal/Neonatal Hydrops
Thomas Jefferson University
55 participants
Jan 15, 2019
OBSERVATIONAL
Conditions
Summary
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.
Eligibility
Inclusion Criteria6
- Fetal hydrops identified anytime in pregnancy after the first trimester
- Parents are planning to proceed with amniocentesis as a routine workup for hydrops.
- Both parents are available for blood sample collection
- Normal CMA and normal karyotype if performed
- Negative workup for Parvovirus B19, cytomegalovirus, toxoplasmosis, and syphilis
- Negative fetomaternal hemorrhage workup as a cause for hydrops For cases of neonatal hydrops, the criteria for invasive prenatal testing will not be required as a postnatal blood sample from the hydropic infant will be the source of proband DNA.
Exclusion Criteria8
- Microarray was abnormal or karyotype was abnormal
- Hydrops caused by congenital infection
- Fetomaternal hemorrhage was a documented etiology for hydrops
- Parental DNA cannot be obtained for either parents
- Donor egg or donor sperm were utilized for conception
- Fetus/Infant diagnosed with lysosomal storage disease
- Pregnant woman or father of the baby less than 16 years of age
- Hydrops was diagnosed concomitantly with intrauterine fetal demise
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Interventions
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 (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.
Locations(1)
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NCT03911531