Replacement of Cytogenetics by aCGH in Prenatal Diagnosis

Overview

Conventional cytogenetics has been the gold standard for chromosomal analysis in prenatal diagnosis. It allows a microscopic examination for any structural abnormalities of chromosome with a turn-around time of 2 to 3 weeks and it is also labour intensive. Array comparative genome hybridisation (aCGH) provides a platform for a higher resolution analysis of chromosomal aberrations in a shorter period of time. The effectiveness of its application in prenatal diagnosis has been examined. The main clinical limitation lies on the difficult interpretation of certain copy number variants (CNV). Our previous study has demonstrated an increase diagnostic yield of 3.2% using aCGH over conventional cytogenetics in the first-tier test study and by 6% as a further test in a cohort of fetuses with ultrasound abnormality and normal karyotype findings. This finding were consistent with the overall reported of 5.2% to 10% increased detection rate by other studies. Various authorities have also approved the use of aCGH as an adjunct diagnostic tool in prenatal cases with fetal ultrasound abnormalities. The presence study aims to demonstrate the clinical acceptability on the use of aCGH to replace cytogenetics in prenatal diagnosis. For patients requiring invasive prenatal diagnosis by chorionic villus sampling or amniocentesis, they will be offered the options of having either conventional cytogenetics or aCGH. A standard unbiased counselling procedure will be performed by well trained midwives. For patients opting for conventional cytogenetics, the current procedure of karyotyping will be performed. For those opting for aCGH, a quantitative fluorescent Polymerase Chain Reaction (PCR) will be performed first to exclude common aneuploidies and triploidies. aCGH will be arranged for those with normal PCR results and conventional cytogenetics will be reserved for visualization of clinically significant CNVs. All patients will be asked to complete the same questionnaire that has been adopted for the study on "Questionnaire survey on Knowledge and Acceptance on Application of whole genome array Comparative Genomic Hybridisation (aCGH) in Prenatal Diagnosis".

Conventional cytogenetics has been the gold standard for chromosomal analysis in prenatal diagnosis. It allows a microscopic examination for any structural abnormalities of chromosome with a turn-around time of 2 to 3 weeks and it is also labour intensive. Array comparative genome hybridisation (aCGH) provides a platform for a higher resolution analysis of chromosomal aberrations in a shorter period of time. The effectiveness of its application in prenatal diagnosis has been examined (Callaway, Shaffer, Chitty, Rosenfeld, \& Crolla, 2013). The main clinical limitation lies on the difficult interpretation of certain copy number variants (CNV). Our previous study has demonstrated an increase diagnostic yield of 3.2% using aCGH over conventional cytogenetics in the first-tier test study and by 6% as a further test in a cohort of fetuses with ultrasound abnormality and normal karyotype findings (Kan et al., 2014). This finding were consistent with the overall reported of 5.2% to 10% increased detection rate by other studies (de Wit et al., 2014; Hillman et al., 2013; Hillman et al., 2011). Various authorities have also approved the use of aCGH as an adjunct diagnostic tool in prenatal cases with fetal ultrasound abnormalities (American College of Obstetricians \& Gynecologists, 2013; Novelli et al., 2012).