Table 1 Clinical information, experimental results, and clinical outcomes of four cases with mosaic chromosomal aneuploidy and UPD

1

A 33-year-old pregnant woman whose fetus had a normal phenotype on ultrasound. Due to a high-risk result for chromosome 2 on cell-free non-invasive prenatal test and reversed alpha wave in the ductus venosus and amniocentesis was performed at nineteen weeks and three days of gestation

Amniocyte

46,XX

The TPOX locus of the fetus in chr2 was a single peak without information, and the D2S1338 locus had three fluorescence peaks (19, 21, and 24 with an area of 5246, 1279, and 5020), and two of them (19 and 21) were the identical sizes with the mothers (Fig. 1A)

The amniocyte microarray results of case 1 showed that chromosome 2 was increased by about 7%. The B Allele Frequency (BAF) indicated the chr2 was a UPD, which consisted of isoUPD and hetUPD, and the proportion of UPD(2) was about 12% (Fig. 2A)

ND

ND

None of pathogenic or likely pathogenic snv/Indel variants were detected

The venous catheter wave was reversed. The fetus had no significant abnormal phenotype and was normal in size

The pregnancy was continued, and the baby was delivered to term. The baby’s growth and development were not abnormal after the follow-up of half a year

2

A 38-year-old pregnant woman. Due to a high-risk result for chromosome 15 on cell-free non-invasive prenatal test and advanced-age and amniocentesis was performed at gestational age 18 + 5

Amniocyte

47,XX,+15[3]/46,XX[125]

The Penta E locus of the uncultured amniocytes in chr15 had three peaks (12, 14, 21 with an area ratio of 1:1:0.4), and two of them (12 and 14) were the identical sizes with the mothers’. The peaks of cultured amniocytes were 12 and 14, with a ratio of 1.2 (Fig. 1B)

The microarray results of the uncultured amniocytes suggested that there was about a 60% increase of the chr15, and the BAF and AD showed several bands (Fig. 2B)

ND

ND

ND

The fetus had no significant abnormal phenotype by Ultrasound

The pregnancy was terminated

3

A 21-year-old pregnant woman. Ultrasound presented with fetal pericardial effusion of 3 mm and an adrenal cystic echo at twenty-three weeks. The amniocentesis proceeded at twenty-three weeks and four days

Amniocyte, fetal tissues (skin, muscles, and kidneys)

45,X[9]/46,XX[70]

Paternal alleles of amniocytes were significantly more than maternal ones because their fluorescence peak ratios were about 1.3–1.5, and paternal heterodisomy was excluded (Fig. 1C)

The microarray results of the amniocytes were arr(X) x1-2, mos UPD(1–22, X). The chrX was less (45,X accounted for about 13%) and mosaic whole genome UPD (about 20%)(Fig. 2C). The chip result (A) showed a decrease of chrX in amniocytes, muscles, and kidneys except for skin. And the mosaic levels of 45,X cells were calculated to be 13%, 25%, and 34%, respectively (Fig. 3)

ND

The MS-MLPA results of 11p15.5 and 15q11-13 regions in amniocytes showed normal

ND

Ultrasound showed the fetus had a pericardial effusion of 3 mm and an adrenal cystic echo at 23 weeks of gestation

The pregnancy was terminated

4

A 35-year-old pregnant woman with a high risk of trisomy 21, due to elevated beta-HCG MOM of 3.24 (reference value is below 2.5) in mid-term pregnancy serum screening. The amniocentesis proceeded at a gestational age of twenty weeks and two days

Amniocyte

47,XY,+20[45]/46,XY[5]

The four single-peak STR of chr20 in the amniocytes (Fig. 1D) were identical to one of the mothers’, indicating their maternal origin.

The CMA results of the uncultured amniocytes showed no copy number variation (CNV) besides isoUPD of chr20 (Fig. 2D1)

Uncultured amniocytes: normal.

Cultured amniocytes: 20% T20 was found (Fig. 2D2)

ND

ND

Ultrasound indicated intrauterine growth restriction after 22 weeks

The pregnancy was terminated