Table 2 Results of cytogenetic testing in fetuses with enlarged NT (≥3.5 mm) or hygroma colli in the first trimester in fetuses referred for cytogenetic testing
Type of chromosome aberration | Number of fetuses n = 362 | Potential detection by current NIPT approaches | % of anomalies that are going to be missed due to placental mosaicism or current testing resolution (>7–10 Mb) |
|---|---|---|---|
Autosomal aneuploidy | Yes | 3.5 % is likely to be missed [20, 49, 50] 0.8 % (3/362) | |
Trisomy 21 | 63 (17 %) | ||
Trisomy 18 | 28 (7.7 %) | ||
Trisomy 13 | 9 (2.5 %) | ||
Sex-chromosomal aneuploidy | Yes (if X/Y analysis are included) | 10 % of monosomy X are likely to be missed [24] 0.5 % (2/362) Mosaic samples are most probably missed 0.5 % (2/362) | |
Monosomy Xa | 20 (5.5 %) | ||
XXX | 2 (0.5 %) | ||
XXY | 1 (0.3 %) | ||
Mosaic X/XY | 2 (0.5 %) | ||
Triploidy | 3 (0.8 %) | Yes (if SNP approach is applied) | Most of the current approaches cannot detect triploidy, and so far it is not possible to combine targeted SNP analysis with high coverage and whole genome profiling with high resolution 0.8 % (3/362) |
Pathogenic unbalanced chromosome aberrations: 1) 46,XY,der [9] t (9;13) (q33.1;q12.11),-13 (NT 4.9 mm; 116 Mb gain at 9p24-q33)) 2) 46,XX,del [8] (p23.1) inv dup [8] (p11.21p23.1) (NT 4.6 mm; 28 Mb gain at 8p) 3) 45,XX,der [4] t (4;15) (q32.1;q13.3),-15dn (hygroma colli; 34 Mb loss at 4p)) 4) arr [hg19] 9p24.3p22.2 (46,587-18,277,618) x1 (NT 5.2 mm; 18 Mb loss at 9p) 5) arr [hg19] 1q32.1q44 (202,542,202-249,218,992) x3,9p24.3p24.1 (46,587-7,017,391) x1 (NT 3.6 mm, 47 Mb gain at 1q, 7 Mb loss 9p) 6) atypical 22q11 microdeletion of paternal origin arr [hg19] 22q11.21 (21,111,299-21,463,730) x1 pat (NT 4.3 mm, >0.5 Mb) | 6 (1.6 %) | Larger than 10 Mb Yes (if whole genome profiling with resolution of 10 Mb is applied) | 1/6 cases would be potentially missed: 0.3 % (1/362) |
Susceptibility loci for neurodevelopmental disorders: 1) 15q11 microdeletion of NIPA1/NIPA2 of paternal origin arr [hg18] 15q11.2 (20,191,584-21,025,923) x1pat (NT 4.7 mm) 2) 15q11 microdeletion of NIPA1/NIPA2 of maternal origin arr [hg19] 15q11.2 (22,299,434-23,272,733) x1mat (NT 4.4 mm) 3) de novo 16q11.2 microdeletion arr [hg19] 16p11.2 (29,595,483-30,198,151) x1dn (hygroma colli) | 3 (0.8 %) | No | So far genome wide detection of submicroscopic aberrations is not feasible. All will be missed 0.8 % (3/362) |
Total number abnormal cases | 137 (38 %) | ||