Maternal Plasma DNA and RNA Sequencing for Prenatal Testing.
Cell-free DNA (cfDNA) testing has recently become indispensable in diagnostic testing and screening. In the prenatal setting, this type of testing is often called noninvasive prenatal testing (NIPT). With a number of techniques, using either next-generation sequencing or single nucleotide polymorphism-based approaches, fetal cfDNA in maternal plasma can be analyzed to screen for rhesus D genotype, common chromosomal aneuploidies, and increasingly for testing other conditions, including monogenic disorders. With regard to screening for common aneuploidies, challenges arise when implementing NIPT in current prenatal settings. Depending on the method used (targeted or nontargeted), chromosomal anomalies other than trisomy 21, 18, or 13 can be detected, either of fetal or maternal origin, also referred to as unsolicited or incidental findings. For various biological reasons, there is a small chance of having either a false-positive or false-negative NIPT result, or no result, also referred to as a "no-call." Both pre- and posttest counseling for NIPT should include discussing potential discrepancies. Since NIPT remains a screening test, a positive NIPT result should be confirmed by invasive diagnostic testing (either by chorionic villus biopsy or by amniocentesis). As the scope of NIPT is widening, professional guidelines need to discuss the ethics of what to offer and how to offer. In this review, we discuss the current biochemical, clinical, and ethical challenges of cfDNA testing in the prenatal setting and its future perspectives including novel applications that target RNA instead of DNA.
Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: s.tamminga@vumc.nl.
Saskia
S
Tamminga
Academic Medical Centre, Amsterdam, The Netherlands.
Merel
M
van Maarle
Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands; EMGO Institute for Health Care Research, VU University Medical Center, Amsterdam, The Netherlands.
Lidewij
L
Henneman
Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.
Cees B M
CB
Oudejans
Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands; EMGO Institute for Health Care Research, VU University Medical Center, Amsterdam, The Netherlands.
Martina C
MC
Cornel
Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
Erik A
EA
Sistermans
D000782:Aneuploidy; D004247:DNA / Q000097:blood* / Q000235:genetics; D005188:False Negative Reactions; D005189:False Positive Reactions; D005260:Female; D005333:Fetus; D005820:Genetic Testing / Q000941:ethics / Q000295:instrumentation / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D033162:Incidental Findings; D020641:Polymorphism, Single Nucleotide; D017410:Practice Guidelines as Topic; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000941:ethics / Q000295:instrumentation / Q000379:methods*; D012313:RNA / Q000097:blood* / Q000235:genetics; D012204:Rh-Hr Blood-Group System / Q000097:blood
D012204:Rh-Hr Blood-Group System; C026410:Rho(D) antigen; D012313:RNA; D004247:DNA
Fetal fraction; Massively parallel sequencing; NIPT; Noninvasive prenatal testing; Prenatal testing; RNA sequencing; cfDNA testing