Supplementary Material: Clinically significant array CMA findings in prenatal samples, not detected by conventional karyotyping

Case No. / Sample type / Indication / G-banding results* / aCGH result* / Interpretation / Final diagnosis / Pregnancy
outcome
1 / Amniotic fluid / Advanced maternal age + abnormal ultrasound findings (single umbilical artery) / 46,XX / arr 17p12(10,451,110x2, 12,023,651-15,415,749x1, 16,622,659x2)mat / 3.4 Mb inherited deletion at 17p12 consistent with Hereditary neuropathy with liability to pressure palsies (HNPP) / MIM disease (162500), Abnormal / Continued
2 / CVS / Advanced maternal age + abnormal ultrasound findings (Cystic Hygroma) / 46,XY / arr 10q26.12q26.3(120,459,257x2, 121,580,323-135,215,585x1)dn / de novo complex rearrangement involving a 13.6 Mb deletion at 10q26.12-10q26.3 and a 14.6 Mb duplication at 16q23.1-q24.3 / Abnormal / TOP
arr 16q23.1q24.3(71,387,225x2, 74,055,794-88,674,700x3 )dn
3 / CVS / Abnormal ultrasound findings (abnormal nuchal translucency) / Cell culture failure / arr 8p23.3p23.1( 115,733-6,615,616x1, 8,235,335x2)dn / de novo complex rearrangement involving a 6.5 Mb deletion at 8p23.3-p23.1 and a 14.6 duplication at 8p22-p21.1 consistent with inv dup del(8p) / Abnormal / TOP
arr 8p22p21.1(11,900,030x2, 12,718,648-27,369,929x3, 28,531,954x2)dn
4 / CVS / Advanced maternal age + abnormal ultrasound findings (abnormal nuchal translucency) / 46,XY / arr 5q35.2q35.3(174,837,770x2, 175,499,944-177,240,560x1, 177,681,483x2)dn / 1.7 Mb de novo deletion at 5q35.2-q35.3, including the NSD1 gene, consistent with Sotos Syndrome / MIM disease (117550), Abnormal / TOP
5 / Amniotic fluid / Advanced maternal age + abnormal ultrasound findings (tetralogy of Fallot) / 46,XX / arr 22q11.21(16,038,711x2, 17,552,769-18,223,647x1, 21,021,548x2)dn / 0.67 Mb de novo deletion at 22q11.21 consistent with 22q11.2 deletion syndrome / MIM disease (188400), Abnormal / TOP
6 / Amniotic fluid / Abnormal ultrasound findings (tetralogy of Fallot) / 46,XX / arr 22q11.21(17,662,989x2, 19,172,842-19,706,824x1, 19,799,866)dn / 0.53 Mb de novo deletion at 22q11.21 consistent with 22q11.2 deletion syndrome / MIM disease (188400), Abnormal / TOP
7 / Amniotic fluid / Advanced maternal age / 46,XY / arr 17p12(13,313,672x2, 14,324,519-15,415,749x3, 16,622,659x2)mat / 1.1 Mb inherited duplication at 17p12 consistent with Charcot-Marie-Tooth neuropathy type 1 A (CMT1A) / MIM disease (118220), Abnormal / Continued
8 / Amniotic fluid / Advanced maternal age / 46,XX / arr 15q13.1q13.3(27,819,621x2, 27,927,504-30,870,822x1, 30,928,648x2)dn / 2.9 Mb de novo deletion at 15q13.1-q13.3, consistent with 15q13.3 microdeletion syndrome / MIM disease (612001), Abnormal / TOP
9 / Amniotic fluid / Advanced maternal age / 46,XX / arr 22q11.21(16,038,711x2, 17,552,769-18,223,647x3, 21,021,548x2)mat / 0,67 Mbinherited duplication at 22q11.21 consistent with 22q11.2 microduplication syndrome / MIM disease (608363), Abnormal / TOP
10 / Amniotic fluid / Advanced maternal age / 46,XX / arr 22q11.21(16,038,711x2, 17,552,769-18,223,647x3, 21,021,548x2)pat / 0,67 Mb inherited duplication at 22q11.21 consistent with 22q11.2 microduplication syndrome / MIM disease (608363), Abnormal / TOP
11 / Amniotic fluid / Advanced maternal age / 46,XY / arr Xp11.3p11.23(43,564,668x1, 45,230,402-48,510,231x0, 48,556,979x1)mat / 3.3 Mb inherited deletion at Xp11.3p11.23 / Abnormal / TOP
12 / Amniotic fluid / Advanced maternal age / 46,XY / arr Xp21.2p21.1(31,239,491x1, 31,491,883-31,694,745x2, 31,832,649x1)mat / 0.2 Mb inheritedduplication at Xp21.2-p21.1, including exons 54-59 of the Dystrophin gene, consistent with Duchenne Muscular Dystrophy (DMD) / MIM disease (310200), Abnormal / TOP
13 / Amniotic fluid / parental anxiety / 46,XY / arr Xp21.2p21.1(31,101,821x1, 31,149,156-31,598,354x2, 31,604,241x1)dn / 0.45 Mb de novo duplication at Xp21.2-p21.1, including exons 56-77 of the Dystrophin gene, consistent with Duchenne Muscular Dystrophy (DMD) / MIM disease (310200), Abnormal / TOP
14 / Amniotic fluid / parental anxiety / 46,XY / arr 17p12p12(13,313,672x2, 14,324,519-15,415,749x3, 16,622,659x2)pat / 0.61 Mb inherited duplication at 17p12 consistent with Charcot-Marie-Tooth neuropathy type 1 A (CMT1A) / MIM disease (118220), Abnormal / Continued
15 / Amniotic fluid / parental anxiety / 46,XX / arr 17p12(14,882,577x2, 15,067,219-15,415,749x3, 16,622,659x2)mat / 0.35 Mb inherited duplication at 17p12 consistent with Charcot-Marie-Tooth neuropathy type 1 A (CMT1A) / MIM disease (118220), Abnormal / Continued
16 / Amniotic fluid / parental anxiety / 46,XY / arr Xq22.2(101,642,281x1, 102,696,222-103,233,743x2, 105,106,632x1)dn / 0.54 Mb de novo duplication at Xq22.2, including the PLP1 gene, consistent with Pelizaeus-Merzbacher disease / MIM disease (312080), Abnormal / TOP
17 / Amniotic fluid / parental anxiety / 46,XY / arr 15q11.2q13.1(21,528,565x2, 21,732,199-25,890,148x1, 27,539,192x2)dn / 4.6 Mb de novo duplication at 15q11.2q13.1, consistent with 15q11-q13 duplication syndrome / MIM disease (608636), Abnormal / TOP
18 / Amniotic fluid / parental anxiety / 46,XX / arr 2p24.3p24.2(12,802,349x2, 14,608,277-17,091,771x1, 18,578,430x2)dn / 2.5 Mb de novo deletion at 2p24.3p24.2, including the MYCN gene, consistent with Feingold syndrome / MIM disease (164280), Abnormal / TOP
19 / CVS / parental anxiety / 46,XX / arr 19q13.41q13.43(54,618,872x2, 56,114,764-63,569,467x3 )dn / 7. 5 Mb de novo duplication at 19q13.41q13.43 / Abnormal / Continued
20 / Amniotic fluid / parental anxiety / 46,XY / arr 15q13.1q13.3(30,032,329x2, 30,140,212-33,279,586x1, 34,101,659x2)dn / 3.1 Mb de novo deletion at 15q13.1-q13.3, consistent with 15q13.3 microdeletion syndrome / MIM disease (612001), Abnormal / TOP
21 / Amniotic fluid / parental anxiety / 46,XY / arr 17p12(14,383,794x2, 14,864,898-15,475,024x3, 16,682,433x2)pat / 0.61 Mb inherited duplication at 17p12consistent with Charcot-Marie-Tooth neuropathy type 1 A (CMT1A) / MIM disease (118220), Abnormal / Continued
22 / CVS / parental anxiety / 46,XX / arr 7q36.1q36.3(151,016,718x2, 151,650,513-158,936,171x3 )dn
arr 9p24.3p23( 104,476-9,751,175x1, 10,659,433x2)dn / de novo complex rearrangement involving a 7,3 Mb duplication at 7q36.1q36.3 and a 9.6 Mb deletion at 9p24.3p23 / Abnormal / TOP
23 / Amniotic fluid / parental anxiety / 46,XY / arr Xp21.1(31,694,745x1, 31,832,649-31,932,608x0, 32,049,231x1)mat / 0.1 Mb inherited deletion at Xp21.1, including exons 48-50 of the Dystrophin gene, consistent with Duchenne Muscular Dystrophy (DMD) / MIM disease (310200), Abnormal / TOP
24 / CVS / Abnormal fetal karyotype (balanced translocation) / 46,XY / arr 6q14.3q15(85,114,738x2, 86,128,448-91,301,783x1, 93,149,125x2)dn / 5.2 Mb de novo deletion at 6q14.3q15 / Abnormal / TOP

*According to International System for Human Cytogenetic Nomenclature (ISCN) 2009; CVS: chorionic villus sampling; TOP: Termination of pregnancy.

Supplementary Material: Clinically significant chromosomal abnormalities detected in prenatal samples by both conventional karyotyping and aCGH

No. of samples / Chromosomal findings / Concordance / Final diagnosis
G-banding results* / aCGH result*
35 / 47,XX,+21 or 47,XY,+21 / arr 21q11.2q22.3(13,452,809-46,844,477x3) / Y / Trisomy 21
9 / 47,XX,+18 or 47,XY,+18 / arr 18p11.32q23(74,461-76,025,499x3) / Y / Trisomy 18
3 / 47,XX,+13 or 47,XY,+13 / arr 13q12.11q34(18,425,650-114,037,803x3) / Y / Trisomy 13
2 / 45,X / arr Xp22.33q28(386,805-154,782,695x1) / Y / Monosomy X
2 / 47,XXX / arr Xp22.33q28( 386,805-154,782,695x3 ) / Y / 47,XXX
2 / 47,XYY / arr Yp11.32q12(386,805-57,461,078x2) / Y / 47,XYY
1 / 47,XXY / arr Xp22.33q28( 386,805-154,782,695x2 ) / Y / 47,XXY
1 / 46,XX[85]/45,X[15] / arr Xp22.33q28(386,805-154,782,695x1) / Y / Monosomy X mosaic
1 / 46,XX[90]/45,X[10] / arr Xp22.33q28(386,805-154,782,695x1) / Y / Monosomy X mosaic
1 / 46,XY[50]/47,XXY[50] / arr Xp22.33q28( 386,805-154,782,695x2 ) / Y / 47,XXYmosaic
1 / 46,XY[62] /47,XY+3[38] / arr 3p26.3q29( 233,708-197,650,296x3 ) / Y / Trisomy 3 mosaic
1 / 46,XX,[80]/46,XX,dup(5)(p15p12)[20] / arr 5p15.33p12(109,395, 234,837-43,988,038x3, 45,195,011x2) / Y / Trisomy 5p mosaic
1 / 46,XX,[94]/46,XX,dup(6)(p25.3p11.1)[6] / arr 6p25.3p11.1( 48,351-58,804,343x3, 62,087,021x2) / Y / Trisomy 6p mosaic
1 / 46,XX[80]/47,XX,+7[20] / arr 7p22.3q36.3(168,315-158,628,932x3) / Y / Trisomy 7 mosaic
1 / 46,XY[80]/47,XY,+18[20] / arr 18p11.32q23( 74,461-76,025,499x3 ) / Y / Trisomy 18 mosaic
1 / 46,XY,[80]/47,XY,+19[20] / arr 19p13.3q13.43( 1,413,529-63,569,467x3 ) / Y / Trisomy 19 mosaic
1 / 46,XY[80]/47,XY,+21[20] / arr 21q11.2q22.3( 13,452,809-46,844,477x3 ) / Y / Trisomy 21 mosaic
1 / 46,XX[65]/47,XX,+22[35] / arr 22q11.1q13.33( 15,398,876-49,265,116x3 ) / Y / Trisomy 22 mosaic
1 / 46,XX,[16]/47,XX,+20[84] / arr(1-22,X)x2 / N / 46,XX
1 / 46,XY,dup(5)(q?) / arr 15q24.2q26.3(73,240,751x2, 73,867,177-100,171,678x3) / N / Duplication 15q24.1-qter
1 / 46,XY,del(8)(p22p21.1) / arr 8p22p21.1(15,628,625x2, 16,397,906-27,369,929x1, 28,531,954x2) / Y / Deletion 8p22-p21.1
1 / 46,XX,dup(15)(q21.2q25.2) / arr 15q21.2q25.2(47,776,589x2, 49,013,732-82,095,991x3, 83,784,667x2) / Y / Duplication 15q21.2q25.2
1 / 46,XY,del(18)(pter->p11.2) / arr 18p11.32p11.21( 74,461-14,066,043x1, 17,197,559x2) / Y / Deletion 18p11.32p11.21
1 / 47,XY,i(12)(p10) / arr 12p13.33p11.1( 251,339-33,361,238x4, 38,998,506x2) / Y / Tetrasomy 12p
1 / 46,X,i(Yp) / arr Yp11.31p11.2( 2,565,871-10,024,245x2, 13,878,340x1)
arr Yq11.21q12(13,878,340x1, 14,160,668-59,000,853x0 ) / Y / Isochromosome Yp

* International System for Human Cytogenetic Nomenclature (ISCN) 2009.

Supplementary Material: CMA detection rates according to the indication for testing in prospective prenatal studies

Indication / Lee et al.29
(n = 3171) / Armengol et al.28
(n = 906) / Other studiesa
(n = 1000) / Current study
(n = 3000) / Combined
(n=8077)
No. of samples (%) / No. of pathogenic CNVs (%) / No. of samples (%) / No. of pathogenic CNVs (%) / No. of samples (%) / No. of pathogenic CNVs (%) / No. of samples (%) / No. of pathogenic CNVs (%) / No. of samples (%) / No. of pathogenic CNVs (%)
Abnormal ultrasound findings / 194 (6.1) / 16 (8.2) / 173 (19.1) / 6 (3.5) / 470 (47.0) / 12 (2.6) / 95 (3.2) / 6 (6.3) / 932 (11.5) / 40 (4.3)
Advanced Maternal Age / 1911 (60.3) / 10 (0.5) / 273 (30.1) / 3 (1.1) / 253 (25.3) / 1 (0.4) / 1118 (37.3) / 6 (0.5) / 3555 (44.0) / 20 (0.6)
Parental anxiety / 989 (31.2) / 5 (0.5) / 60 (6.6) / 1 (1.7) / 93 (9.3) / 0 (0.0) / 1675 (55.8) / 11 (0.7) / 2817 (34.9) / 17 (0.6)
Abnormal fetal karyotype / 51 (1.6) / 3 (5.9) / - / - / 37 (3.7) / 1 (2.7) / 25 (0.8) / 1 (4.0) / 113 (1.4) / 5 (4.4)
Abnormal maternal serum screening test / 26 (0.8) / 0 (0.0) / 235 (26.0) / 1 (0.4) / 11 (1.1) / 1 (9.1) / 29 (1.0) / 0 (0.0) / 301 (3.7) / 2 (0.7)
Family history of a genetic condition / - / - / 145 (16.0) / 3 (2.1) / 136 (13.6) / 3 (2.2) / 25 (0.8) / 0 (0.0) / 306 (3.8) / 6 (2.0)
Cell culture failure / - / - / - / - / - / - / 33 (1.1) / 0 (0.0) / 33 (0.4) / 0 (0.0)
Other / - / - / 20 (2.2) b / 0 (0.0) / - / - / - / - / 20 (0.2) / 0 (0.0)
High risk pregnancies
(Abnormal ultrasound findings+ abnormal fetal karyotype) / 245 (7.7) / 19 (7.8) / 173 (19.1) / 6 (3.5) / 507 (50.7) / 13 (2.6) / 120 (4.0) / 7 (5.8) / 1045 (12.9) / 45 (4.3)
Low risk pregnancies
(Advanced Maternal Age+ Parental anxiety+ Abnormal maternal serum screening test+ Family history of a genetic condition+ Cell culture failure, Other) / 2926 (92.3) / 15 (0.5) / 733 (80.9) / 8 (1.1) / 493 (49.3) / 5 (1.0) / 2880 (96.0) / 17 (0.6) / 7032 (87.1) / 45 (0.6)
Total / 3171 / 34 (1.1) / 906 / 14 (1.5) / 1000 / 18 (1.8) / 3000 / 24 (0.8) / 8077 / 100 (1.2)

aCoppinger at al. 2009; Shaffer et al., 2008; Maya et al., 2010; Van den Veyver et al., 2009; Sahoo et al., 2006. b Includes multiplex pregnancy, viral infection, and other rare indications.

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