Supplemental Material: Index patients –ultrasound abnormalities, material, gestation age and array results. Array results including final conclusion, inclusive de novo (or unknown inheritance) UVs. Polymorphisms and rare private variants are not listed.
Material / Total input DNA ng / gestational age* / Array results1 / hygroma colli / LTC / 80 / 15.1 / Normal
2 / SUA, split hand / uAF / 44 / 20.1 / No results, quality too low probably due to low DNA input
3 / hypertelorism, low set ears, wide mouth, webbing neck, contractures, rocker bottom feet / CB / 100 / 20.2 / Normal
4 / NT (5,5 mm), AVSD, microcephaly / LTC / 77 / 13.1 / Abnormal 936kb loss
arr 15q11.2(19837058-20773130)x1
5 / Foetus 1: no ultrasound abnormalities;
Foetus 2 (tested with HCS):femoral bowing, possible skeletal dysplasia / uAF / 54 / Array request after TOP / Abnormal 2,7Mb loss
arr 17q24.3(65,418,775-68,141,957)x1
6 / left sided diaphragmatic hernia, increased NT, dextroposition heart / uAF / 79 / 20.3 / UVarr 10p12.33(19,004,488-19,278,648)x1 dn
7 / IUFD + MCA, IUGR / uAF / 200 / 24.2 / Normal
8 / encephalocele, hydrothorax, diaphragmatic eventration, TOP / uAF / 169 / 21.5 / Normal
9 / MCA (cleft face, intra-oral membrane, broad neck, abdominal wall defect, bilateral radius aplasia, bilateral cleft hands / LTC / 200 / 13.3 / Normal
10 / IUGR, horse shoe kidney, club feet, pulmonary hypoplasia, anhydramnion, pericardial effusion / uAF / 80 / 20.2 / UV 15 LOH regions >5Mb (parents are cousins)
11 / increased NT, congenital heart defect, IUGR / LTC / 200 / 12.5 / UV arr 21q22.3(46,247,853-46,944,323)x1 ?dn (mother normal, father unavailable)
12 / microcephaly, dysmorphic features, ASD type II, club feet, pulmonary hypoplasia, left isomerism, syndactyly / uAF / 43 / 20.6 / Normal
13 / ectopic kidney, truncus arteriosus, microtia, dysmorphic features / uAF / 129 / 20.3 / UV arr 15q26.3(98,300,313-98,794,497)x3 dn
14 / IUGR, dysmorphic features: exophthalmus, malformations of nose and ears, wide mond, perioral furrows / uAF / 47 / 21.2 / Normal
15 / severe IUGR, ambiguous genitalia, hirsutism / uAF / 57 / 17.2 / Normal
16 / tetralogy of Fallot, hypospadias, microcephaly, dysmorphic features / LTC / 52 / 13.3 / Normal
17 / oesophagal atresia, anal atresia, agenesis of kidneys/bladder, ambiguous genitalia, dysmorphic features / uCB / 150 / Array request afterTOP / Normal
18 / SUA, increased NT, thickening of RV wall, dysmorphic features, pectus excavatum / cF / 200 / Array request after TOP / Normal
19 / anencephaly, unilateral hydrothorax, myocard possibly thickened, jugular sacs, congenital heart malformation, IUFD, sex reversal / LTC / 200 / 11.4 / Normal
20 / IUGR, VSD, SUA, renal agenesis, lateralisation defect / cF / 115 / Array request after TOP / Normal
21 / SUA, prominent heels/rocker bottom feet, micromelia, hydrothorax, complex heart malformation (DORV, TGA, HLHS, ASD1) / uAF / 200 / 21.2 / Normal
22 / hydrothorax, jugular sacs / uAF / 13 / 16.2 / Normal
23 / midfacial cleft/hypoplasia, abnormal intracranial anatomy, potential encephalocele, skull edema, dextrocardia, clubhand left / uAF / 102 / 21.1 / Normal
24 / left sided diaphragmatic hernia, partial AVSD, mild unilateral hydronephrosis / uAF / 18 / 32.2 / Normal
25 / IUGR, echogenic bowel, oligohydramnion, dysmorphic features / cAF / 200 / 21.5 / Normal
26 / lumbal scoliosis, gastroschisis, herniated viscera: bowel, liver, stomach, gall bladder), bilateral polydactyly, omphalocele, amniotic band syndrome / uAF / 200 / 21.2 / Normal
27 / polyhydramnion, hydrops, dysmorphic features / cAF / 200 / 30.4 / Normal
28 / microcephaly, cheilognathopalatoschisis, dysmorphic ears / Blood / 200 / Array request after birth / Normal
29 / gastroschisis / uAF / 200 / 21.4 / Normal
30 / unilateral hydronephrosis / uAF / 86 / 20.4 / Normal
31 / double bubble, polyhydramnion, VSD / uAF / 13 / 30.3 / Normal
32 / oligohydramnion, empty bladder, potential vermis defect, echogenic focus heart, left kidney not visualized / AB / 200 / Array request after TOP / Normal
33 / HLHS, TGA / uAF / 57 / 20.2 / Normal
34 / fetal hydrops / uAF / 42 / 16.3 / Normal
35 / holoprosencephaly, median cheiloschisis, potential absent nasal bone / uAF / 1 / 16.1 / Normal
36 / anhydramnion, megabladder, anal atresia, unilateral renal agenesis, club feet, clinodactyly / cF / 200 / Array request after TOP / Normal
37 / complex cor vitium / uAF / 205 / 20.0 / Normal
38 / IUGR, hydrops, no clear dysmorphic features / uAF / 209 / 23.0 / Normal
39 / MCA (spina bifida, pulmonary right isomerism) / uAF / 3,5 / 16.2 / Normal
40 / hygroma colli 8.5 mm, potential heart malformation / LTC / 104 / 13.3 / Normal
41 / HLHS / uAF / 200 / 15.5 / Normal
42 / diaphragmatic hernia , XY female / Blood / 200 / Array request after birth / Normal
43 / Heart malformation LVOT / uAF / 75 / 21.6 / Normal
44 / complex heart malformation, hygroma colli, lateralisation defect / cAF / 200 / Array request after TOP / Normal
45 / HLHS / uAF / 200 / 21.4 / UV arr 5q22.3q23.2(115,110,617-123,475,624)x2 hmz
46 / interhemisferic cyst / uAF / 171 / Array request after TOP / Normal
47 / IUGR, preauricular tag, porencephaly, ventriculomegaly, autopsy revealed intraventricular bleeding / uAF / 152 / Array request after TOP / Normal
48 / small OFC, echogenic focus heart / uAF / 57 / 22.0 / Normal
49 / HLHS and aortic stenosis / uAF / 146 / Array request after TOP / Normal
50 / brachycephaly, distal vermisdefect, hygroma colli, wide subdural space, nasal bone absence, small nose, prominent heels, widely spread fingers, clinodactyly, hernia diafragmatica left, dextrocardy, AVSD, overriding aorta / uAF / 179 / 20.6 / UV arr 7q31.33( 125,887,720- 126,254,817)x1 dn
51 / plexus choroïdeus cystes, increased NT, echodens focus heart, unilateral pes equinovarus, IUGR, oligohydramnion / uAF / 89 / 21.3 / Abnormal 591kb loss arr 22q11(19,367,716-19,959,004)x1 mat
52 / unilateral pes equinovareus, unilateral radius aplasia with oligodactyly, extreme hydrocephaly, bilateral cheilognatopalatoschisis / uAF / 23.5 / 15.3 / UV 4 LOH regions >5Mb (due to consanquinity)
53 / microcephaly, occipital encephalocele, semilobar holoprosencephaly, proboscus / uAF / 10 / 14.4 / Normal
54 / cheiloschisis left, borderline ventriculomegaly / uAF / 80 / 21.0 / Normal
55 / hygroma colli / LTC / 80 / 11.6 / UV arr 1p33p32.3(47,413,772-55,255,872)x2 hmz,15q13.1q13.2(26,800,867-28,269,872)x3 dn
56 / macrocephaly, abnormal cerebral anatomy, polyhydramnion / uAF / 90 / Array request after TOP / Normal
57 / NT (8,9 mm), hydrops foetalis, hygroma colli, pleural effusion / LTC / 184 / Array request after TOP / Normal
58 / increased NT / cAF / 200 / 21.0 / UV arr 5p15.33p15.2(3,253,425-8,508,645)x2 hmz
59 / hydrops foetalis, hydrothorax and ascites / uAF / 50 / 19.6 / Normal
60 / Foetus 1 (tested with HCS): SUA, extreme IUGR, echodens bowel, pericardial effusion;
Foetus 2: no ultrasound abnormalities / uAF / 52 / 17.5 / Abnormal2.1Mb loss arr 22q11(17,249,767-19,313,562)x1 dn
61 / severe IUGR; unilateral pes equinovarus, enlarged bowel, hypoplastic cerebellum / uAF / 200 / 21.1 / UV 6 LOH regions >5Mb (due to consanquinity)
UV arr 15q14(32,479,619-32,629,972)x0
NB. Physical positions of the breakpoints utilize the hg18 build of the human genome sequence. Blood was tested in cases where prenatal material was no more available.
* gestational age at the time of punction (week.days)
AB– Abortus material
uCB– uncultured Cord Biopt
CB– Cord Blood
UV– UnclassifiedVariant
cAF–cultured Amniotic Fluid
uAF–uncultured Amniotic Fluid
LTC – Long Term Culture chorion villi
cF - cultured Fibroblasts
HLHS- Hypoplastic Left Heart Syndrome
TGV- Transposition of the Great Vessels
IUGR- Intra Uterine Growth Retardation
IUFD - Intra Uterine Fetal Death
LVOT –Left Ventricle Outflow Tract
ASD1– Atrium Septum Defect type I
RV– Right Ventricle
VSD – Ventricle Septum Defect
AVSD – Atrio-Ventricular Defect
DORV– Double Outlet Right Ventricle
NT- Nuchal Translucency