recommended that all pregnant women be offered non-invasive prenatal testing (NIPT) regardless of the patient's risk profile. 1 With increasing NIPT uptake, encounters with genetic conditions other than the 3 common fetal trisomies are becoming prevalent. We report 2 cases of fetal mosaicisms for chromosomes 13 and 22, respectively.Case 1. The patient was 37 years old and opted for NIPT at 12 weeks (w). Cell-free DNA from maternal plasma was extracted for subsequent low-pass whole genome sequencing. Results showed high risk for trisomy 13, while Y-chromosomal sequences were detected, indicating a male fetus. Fetal fraction was 10.7%. Amniocentesis was performed at 16w, and karyotype showed mosaic 47,XY,+13[3]/46,XY[36] (Fig. 1A). Trisomy 13 mosaicism was diagnosed with 7.7% abnormal cells. She was referred for genetic counselling (GC) and extensively counselled that the fetus is at increased risk of systemic structural abnormality and intellectual disability. After GC and fetal ultrasound scan, the patient decided to proceed with termination of pregnancy (TOP) at 19w.Case 2. The patient was 40 years old and an early scan showed no obvious structural abnormality. At 12w, she opted for NIPT and the blood was processed in the same way as in Case 1. NIPT results showed high risk for trisomy 22, and no Y-chromosomal sequences were detected, indicating a female fetus. Fetal fraction was 11.3%. Amniocentesis was performed at 15w, and karyotype showed mosaic 47,XY,+22[3]/46,XX[12] (Fig. 1B). Low-level trisomy 22 mosaicism was diagnosed with 20.0% abnormal cells. She was referred for GC and counselled on the fetal risk of hemihypertrophy, cardiac defects and development issues. Patient decided to wait for anomaly scans to screen for structural defects before proceeding with TOP. Fetal ultrasonographies at 17-19w showed a growth-restricted fetus with all parameters <1%. There was no obvious structural abnormality seen at that stage. A repeat ultrasonography done at 22w confirmed a severely growth-restricted fetus. The patient underwent medical TOP at 23w.Both patients were referred for GC when the diagnosis was made. For case 1, she was seen by a genetic

The current gold standard for the definitive diagnosis of fetal aneuploidy uses either chorionic villus sampling (CVS) or amniocentesis, both of which are which are invasive procedures carrying a procedure-related risk of miscarriage of up to 0.1%–0.2%. Non-invasive prenatal diagnosis using fetal nucleated red blood cells (FNRBCs) isolated from maternal peripheral venous blood would remove this risk of miscarriage since these cells can be isolated from the mother’s blood. We aimed to detect whole-chromosome aneuploidies from single nucleated fetal red blood cells using whole-genome amplification followed by massively parallel sequencing performed on a semiconductor sequencing platform. Twenty-six single cells were picked from the placental villi of twelve patients thought to have a normal fetal genotype and who were undergoing elective first-trimester surgical termination of pregnancy. Following karyotyping, it was subsequently found that two of these cases were also abnormal (one trisomy 15 and one mosaic genotype). One single cell from chorionic villus samples for two patients carrying a fetus with trisomy 21 and two single cells from women carrying fetuses with T18 were also picked. Pooled libraries were sequenced on the Ion Proton and data were analysed using Ion Reporter software. We correctly classified fetal genotype in all 24 normal cells, as well as the 2 T21 cells, the 2 T18 cells, and the two T15 cells. The two cells picked from the fetus with a mosaic result by CVS were classified as unaffected, suggesting that this was a case of confined placental mosaicism. Fetal sex was correctly assigned in all cases. We demonstrated that semiconductor sequencing using commercially available software for data analysis can be achieved for the non-invasive prenatal diagnosis of whole-chromosome aneuploidy with 100% accuracy.