ABSTRACT
Objective:
To investigate the prenatal management for pathogenic copy number variation (CNV) by analyzing the parental origin of CNV and
pregnancy outcomes in 56 pedigrees.
Methods:
This study retrospectively analyzed the information of
patients who received interventional
prenatal diagnosis and chromosomal
microarray analysis (CMA) at Guangzhou
Women and
Children's Medical Center from January 2015 to December 2020. The cases with pathogenic CNV indicated by CMA and receiving parental CMA for further verification were finally enrolled. Clinical data including prenatal diagnostic indications, chromosomal distribution of the pathogenic fragments and fragment sizes were collected and analyzed using t test. All cases were followed up by
telephone and
record review.
Results:
Fifty-six cases were included in this study. Pathogenic CNV in 13 (23.2%, 13/56)
fetuses were inherited from one
parent (eight from
mothers and five from
fathers), and mainly located in
chromosomes 22 (3/13), 17 (3/11), 16 (2/7), 1 (2/4), and X (3/6) with fragment sizes all less than 3 Mb. The fragment size of inherited pathogenic CNV was significantly smaller than that of de novo CNV [1.69 (1.36-2.22) vs 7.54 (2.11-12.30) Mb, t=3.47, P=0.001]. Among the 43 cases with de novo pathogenic CNV, seven (16.3%) were
lost to follow up and 35 (97.2%) terminated the
pregnancy. The other one with a 0.58 Mb microruplication at 16p11.2 indicated at 37 gestational weeks gave
birth to a baby weighting 2 900 g at 39 gestational weeks and no
abnormalities were reported during an eight-month
telephone follow-up. Two out of the 13 cases with inherited pathogenic CNV were
lost to follow up and six
pregnancies were terminated. The other five
pregnancies were continued and babies were delivered with no
abnormalities during a median follow-up period of 13 (4-15) months.
Conclusion:
Pathogenic CNV alone should not be the indication for
pregnancy termination.