Clinical Institute of Medical Genetics (CIMG), University Medical Centre Ljubljana, Ljubljana, Slovenia.
Department of Perinatology, Division of Gynaecology and Obstetrics, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Mol Genet Genomic Med. 2019 Jun;7(6):e658. doi: 10.1002/mgg3.658. Epub 2019 Apr 19.
The implementation of molecular karyotyping has resulted in an improved diagnostic yield in the genetic diagnostics of congenital anomalies, detected prenatally or after the termination of pregnancy. However, the systematic epidemiologic ascertainment of copy number variations in the etiology of congenital anomalies has not yet been sufficiently explored.
Consecutive fetuses, altogether 204, with major single or multiple congenital anomalies were ascertained by using the SLOCAT registry for the period from 2011 to 2015. After excluding aneuploidies by using conventional karyotyping or Quantitative Fluorescence-Polymerase Chain Reaction, array comparative genomic hybridization was performed for the detection of copy number variations.
We identified pathogenic or likely pathogenic copy number variations in 14 fetuses (6.8%); 2.9% in fetuses with isolated, and 3.9% in fetuses with multiple congenital anomalies. Additionally, aneuploidies and major structural chromosomal abnormalities were detected in 40.2%.
Our systematic approach of ascertaining congenital anomalies resulted in explaining the etiology of congenital anomalies in 47% of fetuses after the termination of pregnancy. By using array comparative genomic hybridization, we found that copy number variations represent an important part in the etiology of multiple, as well as isolated congenital anomalies, which indicates the importance of analyzing copy number variations in the diagnostic approach of fetuses with congenital anomalies after the termination of pregnancy.
分子核型分析的实施提高了先天性畸形遗传诊断的诊断率，这些畸形可在产前或妊娠终止后被检测到。然而，先天性畸形病因中拷贝数变异的系统流行病学研究尚未得到充分探索。
从 2011 年到 2015 年，使用 SLOCAT 登记系统连续确定了 204 例主要有单一或多种先天性畸形的胎儿。在使用常规核型分析或定量荧光聚合酶链反应排除非整倍体后，进行比较基因组杂交以检测拷贝数变异。
我们在 14 例胎儿（6.8%）中发现了致病性或可能致病性的拷贝数变异；在孤立性先天性畸形胎儿中为 2.9%，在多发性先天性畸形胎儿中为 3.9%。此外，还检测到 40.2%的胎儿存在非整倍体和主要结构性染色体异常。
我们对先天性畸形进行系统确定的方法，在妊娠终止后解释了 47%胎儿的先天性畸形病因。通过使用比较基因组杂交，我们发现拷贝数变异是多发性和孤立性先天性畸形病因的重要组成部分，这表明在妊娠终止后分析先天性畸形胎儿拷贝数变异在诊断方法中的重要性。
