Abstract 60: Effect of Organ Transplantation on the Interpretation of Cell-free Fetal DNA Results

Conference Paper

Abstract Number: 690 Description: A 20-year-old African American female presented for routine fetal anatomy at our Fetal Diagnostic Center. The patient's medical history is complicated by congenital biliary atresia for which she underwent liver transplantation within the first five years of life. The ultrasound revealed a large fetal omphalocele, large ventricular septal defect with both pulmonary artery and aorta originating from the right ventricle and bilateral club feet. Fetal genitalia appeared female. Gestational age was established by ultrasound dating on the day of the exam and was estimated to be 19 weeks, 3 day. The risk of aneuploidy was discussed with the patient; she was offered prenatal screening and/or prenatal diagnosis and declined. Follow-up ultrasound performed at 24 gestational weeks revealed no additional anomalies and no evidence of growth restriction. The patient returned to clinic and elected to have cell-free fetal DNA (MaterniT21 Plus) screening. Results demonstrated an increase copy number of chromosome 18, consistent with Trisomy 18. Y chromosome material was present, consistent with a male fetus. The sample was run again and the presence of Y material was confirmed. Given the constellation of fetal anomalies and the discrepancy between ultrasound appearance of fetal genitalia and cell free fetal DNA results, a limited exam to re-evaluate the fetal genitalia was offered. The genitalia appeared to be unambiguously female. The patient was again offered amniocentesis, which she declined. The pregnancy resulted in an intrauterine fetal demise at 36 weeks, 1 day. Gross evaluation of the fetus revealed clenched hands with overlapping fingers, omphalocele, rocker bottom feet and female genitalia. Microarray performed on tissue obtained postmortem revealed 47,XX+18. Given the patient's history of liver transplantation, we suspected that the patient was the recipient of a male donor's liver and that this could explain the presence of Y chromosome material detected in cell-free fetal DNA. Liver is a highly regenerative tissue and we proposed that the high turnover of liver cells and apoptosis of cellular material, particularly DNA, explains the presence of Y chromosome material. With the patient's consent, we were able to obtain her United Network of Sharing (UNOS) number, contacted the organization and learned that the donor of the liver was male. A review of published medical literature (PubMed, Embase, Scopus, Web of Science, CINAHL) reveals no human case reports of human organ transplantation influencing cell-free fetal DNA prenatal screening results. Our review revealed only research conducted describing methods to detect microchimerism expression of transplanted organs and hypotheses for how their methods could be applied in a clinical testing scenario. The potential for a transplanted organ to affect results should be considered in technologies that utilize human DNA to provide or support clinical management. Our case is the first known to illustrate the effects of organ transplantation on prenatal cell free fetal DNA analysis and the complex genetic counseling involved. This is an important factor to consider in cases where patients with organ transplantation are interested in pursuing cell-free fetal DNA. Keywords: Counseling Cytogenetics Microarray Noninvasive prenatal diagnosis/screening Prenatal Diagnosis Transplantation Ultrasound Primary Topic Focus: Perinatal Genetics Secondary Topic Focus: Genetic Counseling

Full Text

Duke Authors

Cited Authors

  • Nunez, KP; Boyd, B; Livingston, EG

Published Date

  • 2015

Published By

Place of Publication

  • Salt Lake City, UT

Conference Name

  • ACMG Annual Clinical Genetics Meeting

Conference Location

  • First Author: Kristin Paulyson Nunez, M.S Duke University Medical Center Durham, NC Co-Author(s): Brita K. Boyd, MD Duke University Medical Center Durham, NC Elizabeth G. Livingston, MD Duke University Medical Center Durham, NC