Quantitative Fluorescent Polymerase Chain Reaction versus Cytogenetics: Risk-Related Indication and Clinical Implication of Nondetected Chromosomal Disorders

Abstract

Background: The rapid detection of aneuploidies by quantitative fluorescent polymerase chain reaction (QF-PCR) allows reliable prenatal diagnosis of trisomies 21, 18, and 13. Discussion has been raised as to whether single QF-PCR could be an alternative to traditional cytogenetic karyotyping for certain referral categories. Objective: To evaluate an indication-based classification of cases at risk of missing clinically relevant chromosomal disorders by QF-PCR. Methods: From October 1999 to November 2003, 4,682 of 14,123 patients referred for amniocentesis decided to have QF-PCR as a rapid adjunct to conventional cytogenetic evaluation. Patients were classified according to the risk of missing chromosomal abnormalities by QF-PCR based on anamnestic risk and ultrasound prior to amniocentesis. The results in these two defined categories were compared in relation to the clinical significance of cytogenetic results. Results: QF-PCR and conventional cytogenetic analysis had concordant results in 4,617 of 4,682 (98.6%) cases. Thirty-six of 110 (32.2%) clinically significant chromosomal abnormalities were missed by QF-PCR. Patients classified not to be at risk of missing chromosomal abnormalities using QF-PCR had a residual risk of 1/166 (0.6%) for chromosomal distortions of clinical significance. Conclusion: Classification by anamnestic and sonographic data does not specifically identify patients at risk of structural abnormalities. Clinical relevance of the nondetected anomalies essentially justifies traditional karyotyping regardless of risk classification.

Non-invasive prenatal screening versus prenatal diagnosis by array comparative genomic hybridization: a comparative retrospective study

“…Similar to what is observed with NIPS, rapid testing (e.g. QF‐PCR) for the frequent trisomies as a standalone test had been discussed as an alternative to karyotype analysis, but it would miss up to 30% of chromosomal abnormalities depending on the referral indication . When combined screening was introduced, 17% of obstetricians reported that they were offering it as an alternative to amniocentesis (i.e.…”

The detection of chromosome anomalies by QF‐PCR and residual risks as compared to G‐banded analysis

“…Abnormalities such as translocations, deletions, inversions, supernumerary markers, mosaicism, and rare aneuploidies, all of which are detected by G‐banding, are not detectable by QF‐PCR. The detection rate of QF‐PCR versus G‐banded analysis has been studied by numerous groups (Leung et al , 2004; Caine et al , 2005; Ogilvie et al , 2005; Kozlowski et al , 2006; Kagan et al , 2007; Sparkes et al , 2008; Speevak et al , 2008), with results indicating the residual risk of a chromosome abnormality not detected by QF‐PCR in the range of 0.5 to 1.0%.…”

Validation of QF-PCR for Rapid Prenatal Diagnosis of Common Chromosomal Aneuploidies in Korea

“…Rapid prenatal detection of numerical chromosome abnormalities by quantitative fluorescent polymerase chain reaction (QF-PCR) allows for reliable prenatal diagnosis of trisomies 13, 18, and 21 1,2) . QF-PCR is an alternative method for rapid aneuploidy detection (RAD) of common aneuploidies based on the amplification of chromosome-specific DNA short-tandem-repeat (STR) polymorphisms, offering an attractive alternative to fluorescent in situ hybridization (FISH).…”