Chromosomal mosaicism detected by karyotyping and chromosomal microarray analysis in prenatal diagnosis

Abstract

To investigate the incidence and clinical significance of chromosomal mosaicism (CM) in prenatal diagnosis by G-banding karyotyping and chromosomal microarray analysis (CMA). This is a single-centre retrospective study of invasive prenatal diagnosis for CM. From 5758 karyotyping results and 6066 CMA results, 104 foetal cases with CM were selected and analysed further. In total, 50% (52/104) of foetal cases with CM were affected by ultrasound-detectable phenotypes. Regardless of whether they were singleton or twin pregnancies, isolated structural defects in one system (51.35%, 19/37 in singletons; 86.67%, 13/15 in twins) and a single soft marker (18.92%, 7/37 in singletons; 13.33%, 2/15 in twins) were the most common ultrasound anomalies. Mosaic autosomal trisomy (19.23%, 20/104) was the most frequent type, and its rate was higher in phenotypic foetuses (28.85%, 15/52) than in non-phenotypic foetuses (9.62%, 5/52). There was no difference in mosaic fractions between phenotypic and non-phenotypic foetuses based on specimen sources or overall classification. Discordant mosaic results were observed in 16 cases (15.38%, 16/104) from different specimens or different testing methods. Genetic counselling and clinical management regarding CM in prenatal diagnosis remain challenging due to the variable phenotypes and unclear significance. Greater caution should be used in prenatal counselling, and more comprehensive assays involving serial ultrasound examinations, different specimens or testing methods verifications and follow-up should be applied.

Keywords: chromosomal microarray analysis; chromosomal mosaicism; genetic counselling; karyotyping; prenatal diagnosis.

FIGURE 1

Flow diagram of the chromosomal results in 104 foetal cases with mosaicism. A total of 104 foetal cases were recruited, including 85 singleton pregnancies and 19 pairs of twin pregnancies. Among, forty‐three cases only underwent G‐banding karyotyping, 33 cases only underwent CMA, and 28 cases underwent both karyotyping and CMA. In twin pregnancies, only one foetus was affected by ultrasound anomalies in each pair. In addition, the chromosomal results of the affected foetuses were also reported. Other mosaic abnormal karyotypes refer to abnormal karyotypes detected by G‐banding karyotyping such as isochromosomes and marker chromosomes, not including aneuploidies. CMA, chromosomal microarray analysis; US, ultrasound; No. of, the number of; T, Trisomy; CNVs, copy number variants

FIGURE 2

Indications of invasive prenatal diagnosis in foetuses with mosaicism. The sum of the number of cases for different indications exceeds the total number of whole cases (104 cases) because more than one indication may be identified in each case. NIPT, non‐invasive prenatal testing; IUFD, intrauterine foetal death; FGR, foetal growth restriction, n, the number of cases. Parental chromosomal abnormalities include maternal and/or paternal chromosomal abnormalities such as balanced translocation. Ultrasound anomalies include foetal structural defects, soft markers and FGR

FIGURE 3

Incidences of the detailed types of mosaicisms detected in this study. Comparisons for mosaic types were performed between cases with and without ultrasound phenotypes, and Chi‐square tests were used and all P values are two‐sided. Mosaic chromosomal abnormalities were divided into three types: numerical abnormalities, unbalanced structural abnormalities and other. The rate of autosomal trisomy in cases with ultrasound anomalies was higher than that in cases without (*P = 0.023 < 0.05). YES, cases with ultrasound anomalies; NO, cases without ultrasound anomalies; LOH, loss of heterozygosity; n, the number of cases