First: summary and comparison of the results of karyotyping and CNV-seq.
4142 cases of 4230 were analyzed by karyotyping successfully (88 cases failed), with a success rate of 97.92%. 4229 cases were successfully analyzed by CNV-seq (1 case failed), with a success rate of 99.98%. Karyotyping results included 235 cases of aneuploidies, 18 cases of mosaic aneuploidies, 30 cases of large deletions/duplications, 133 cases of balanced rearrangements, 88 cases of suspicious structure changes, 94 cases of polymorphism and 3544 cases of normal. CNV-seq results included 240 cases of aneuploidies, 22 cases of mosaic aneuploidies, 79 cases of pCNVs, 93 cases of VOUS, 102 cases of bCNVs and 3693 cases of normal. The results that lead to birth defects are defined as abnormalities. They included aneuploidy, mosaic aneuploidy, large deletions/duplications and pCNVs. The summary and comparison of all karyotyping and CNV-seq results are shown in table 1.
A total of 283 cases of abnormalities were identified by karyotyping and CNV-seq simultaneously(table 1 red), which included 235 cases of aneuploidies, 18 cases of mosaic aneuploidies, 30 cases of large deletions/duplications or pCNVs. A total of 58 cases of abnormalities were identified by CNV-seq alone(table 1 green), which included 5 cases of aneuploidies, 4 cases of mosaic aneuploidies and 49 cases of pCNVs. Aneuploidies and mosaic aneuploidies were identified by Karyotyping and CNV-seq simultaneously (table 2): 131 cases of trisomy 21(including 2 cases of mosaics), 39 cases of trisomy18, 26 cases of 47,XXY (including one mosaic), 19 cases of monosomy X (including 11 cases of mosaics), 18 cases of 47, XXX, 14 cases of 47,XYY, 3 cases of trisomy 13 (including 2 cases of mosaics), 1 case of mosaic trisomy 22, 1 case of mosaic trisomy 15, 1 case of 48,XXYY. Aneuploidies and mosaic aneuploidies were identified by CNV-seq alone (table 2): 5 cases of trisomy 21(including 1 case of mosaic, mos0.25), 1 case of 47,XXX, 1 case of mosaic 47,XXY (mos0.2) (normal karyotype), 1 case of mosaic trisomy 7 (mos0.1) (normal karyotype), and 1 case of mosaic trisomy 9 (mos0.3) (normal karyotype).
79 cases of large deletions/duplicaitons or pCNVs are shown in table S1. Cases 1-30 with abnormalities were identified by CNV-seq and karyotyping simultaneously(a total of 30 cases). Cases 31-79 with abnormalities were identified by CNV-seq alone (a total of 49 cases). The karyotyping results of 79 cases with CNV-seq results of pCVNs were large deletion/duplication (30 case, case 1~30), suspicious change(13 cases, case 31~43), polymorphism(1 cases, case 44), balanced structural change(2 cases, case 45~46) and normal(33 cases, case 47~79). Among 79 cases of pCNVs, there were 4 cases of monogenic disease (steroid sulphatase deficiency) and 43 cases of identified chromosome disease syndrome. This included 9 cases of 22q11 duplication syndrome, 7 cases of 22q11 deletion syndrome (DiGeorge syndrome), 3 cases of 7q11.23 duplication syndrome, 2 cases of 2q37monosomy syndrome, 2 cases of Cri du Chat Syndrome (5p deletion), 2 cases of Williams-Beuren Syndrome, 2 cases of 8p23.1 deletion syndrome, 2 cases of 18p deletion syndrome, and all other cases of 14 types of chromosome disease syndromes. The summary and comparison of all structural abnormalities are shown in Table 3.
Table S2 showed 102 cases of bCNVs(case 1~102), 93 cases of VOUS(case 103~195) of CNV-seq and corresponding karyotype results. In the samples with CNV-seq results of bCNVs, the karyotyping results were the suspicious change (1 case, case 1), normal (89 cases, case 2~90), polymorphism (5 cases, case 91~95), balanced structural change (7 cases, case 96~102). In the samples with CNV-seq results of VOUS, the karyotyping results were the balanced structural change(6 cases, case 103~108), suspicious change (4 cases, case 109~112), normal(79 cases, case 113~191), failed(4 cases, case 192~195). In this study, 14.39% (20/139) of the balanced rearrangements accompanied by unbalanced structural changes were identified by CNV-seq, including 7 cases of pCNVs (cases 39~45 in table S1), 7 cases of bCNVs (cases 96~102 in table S2) and 6 VOUS (cases 103~108 in table S1).