Konialis Christopher, Pangalos Constantinos
Department of Molecular Genetics and Genomics, InterGenetics - Diagnostic Genetic Centre, Athens, Greece.
Fetal Diagn Ther. 2015;38(3):218-32. doi: 10.1159/000368604. Epub 2015 Jan 30.
The aim of this article is to provide a perspective of prenatal chromosomal diagnosis (PCD) derived from a single center's evolving experience from ∼90,000 consecutive prenatal cases and to highlight important issues and current dilemmas.
Prenatal cases in this study (1985-2013) were referred for various indications, and PCD was performed by standard karyotype in 84,255 cases, multiplex ligation-dependent probe amplification (MLPA) panel in 3,010 cases and standalone array comparative genomic hybridization (aCGH) in 3,122 cases.
Classic karyotype revealed 1.7 and 7.9% of pathological cases in amniotic fluid and CVS samples, respectively, with common aneuploidies accounting for 59.6 and 64.3% of the total abnormal. Molecular approaches increased the diagnostic yield by 0.6% for MLPA and 1.6% for aCGH, uncovering pathogenic chromosomal abnormalities undetectable by karyotype analysis.
Current molecular diagnostic capabilities and the recent introduction of noninvasive prenatal testing (NIPT) point to one current major dilemma in PCD, with serious implications in genetic counseling, relating on the one hand to reaping the benefits from the high detection rate afforded through aCGH but accepting an invasive risk, and on the other hand, offering a lower detection rate practically only for Down syndrome, with minimal invasive risk.
本文旨在从一个单一中心约90,000例连续产前病例不断演变的经验出发，提供产前染色体诊断（PCD）的视角，并突出重要问题和当前困境。
本研究中的产前病例（1985 - 2013年）因各种指征转诊，84,255例采用标准核型分析进行PCD，3,010例采用多重连接依赖探针扩增（MLPA）检测，3,122例采用独立的阵列比较基因组杂交（aCGH）检测。
经典核型分析显示羊水和绒毛取样（CVS）样本中病理病例分别占1.7%和7.9%，常见非整倍体分别占总异常的59.6%和64.3%。分子方法使MLPA的诊断率提高了0.6%，aCGH提高了1.6%，发现了核型分析无法检测到的致病性染色体异常。
当前的分子诊断能力以及最近引入的无创产前检测（NIPT）指出了PCD当前的一个主要困境，这在遗传咨询方面具有严重影响，一方面是要从aCGH提供的高检测率中获益但要接受侵入性风险，另一方面是实际上仅对唐氏综合征提供较低的检测率且侵入性风险极小。
