Analysis of chromosomal abnormalities in 107 fetuses with conotruncal defects using low coverage whole-genome sequencing

Objective To investigate chromosomal abnormalities in fetuses with conotruncal defects(CTD). Methods From January 2013 to February 2017, 107 fetuses (singleton pregnancy) prenatally diagnosed as CTD in Beijing Anzhen Hospital were enrolled. Umbilical cord specimens of these fetuses were collected after termination of pregnancy and analyzed by low coverage whole gene sequencing to detect chromosomal aneuploidy and copy number variations. Types of chromosomal abnormalities in these cases were analyzed. Chi-square test was used for statistical analysis. Results Twenty-two cases (21%, 22/107) were identified with chromosomal abnormalities. The most common seen chromosomal abnormalities were found in those with interrupted aortic arch (2/2), followed by those with tetralogy of Fallot and pulmonary atresia/stenosis accompanied with ventricular septal defect (28%, 12/43). No chromosomal abnormalities were detected in fetuses with aortopulmonary septal defect (0/2). Differences were shown in the detection rates of chromosomal abnormalities among different types of CTD (χ2=12.744, P=0.026). Among the 22 fetuses with chromosomal abnormalities, there were seven with abnormal aneuploidy (three trisomy-13s, two trisomy-18s, one trisomy-21 and one 45,X) and 15 with pathogenic copy number variations [11 cases with 22q11.2 microdeletion syndrome, two with 17p12p11.2 microdeletion (Smith-Magenis syndrome), one with 8p23.3p21.3 microduplication and one with 2p23.1p25.2 microdeletion]. Of the 15 cases with pathogenic copy number variations, 12 segments of microdeletion/microduplications were de novo and one was paternally inherited, while the causes of the other two were not clear because their parents refused chromosomal testing. Conclusions Fetal CTD are likely to be accompanied with aneuploidy abnormalities and chromosome microdeletions/microduplications and the detection rate of chromosomal abnormalities varied with the type of CTD. Microdeletion and microduplication, especially de novo microdeletions/duplications, are the common chromosomal abnormalities. Chromosome analysis is recommended for fetuses prenatally diagnosed with CTD. Key words: Cardiovascular abnormalities; Chromosome aberrations; Chromosome deletion; Aneuploidy; DNA copy number variations