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).