Table 4

Mutation-positive samples (cohorts 1 and 2) and the detected ultrasound findings

CaseGeneGenomic changeProtein changeNGS panel De novo PathogenicityNT (mm)Persistent NTJLSHydrops fetalisPleural effusionAscitesCardiac anomaliesRenal anomaliesPolyhydramniosOther anomaliesPregnancy outcome
1 PTPN11 c.124A>GThr42Ala+?POedema around fetus at 10 weeks+−−−−−−−−Live birth, deceased at age 2
2 PTPN11 c.179G>TGly60Val++P8.6++++−Pericardial effusion, DORV−−Lemon-shaped headToP
3 PTPN11 c.179G>TGly60Val++P8.9++−−−AVSD−−Abnormal skullToP at 21 weeks
4 PTPN11 c.182A>GAsp61Gly+?POedema around fetus at 11 weeks+++−−AVSD, hypoplastic left heartPyelectasis−−ToP
5 PTPN11 c.184T>GTyr62Asp−+P6.1−−−−−−−Mild 34 weeks−Live birth
6 PTPN11 c.184T>GTyr62Asp−+P11.0+−−−−−−−−ToP
7 PTPN11 c.184T>GTyr62Asp++P9.8−−++−−−−−ToP at 16 weeks
8 PTPN11 c.213T>GPhe71Leu++LPIncreased+−+−−−−−−ToP at 14 weeks
9 PTPN11 c.214G>TAla72Ser−+P9.3++−−−Hypoplastic right heart, small triscuspid valve−−−ToP at 23 weeks
10 PTPN11 c.214G>CAla72Pro++LP8.1+−+++−−−−ToP
11 PTPN11 c.215C>TAla72Val−+LP7.0−−−−−−−−−ToP at 16 weeks
12 PTPN11 c.228G>TGlu76Asp−− matP5.7−−−−−AVSD, hypoplastic left heart−−−ToP at 21 weeks
13 PTPN11 c.417G>CGlu139Asp++P6.0+−++−−−−−ToP at 17 weeks
14 PTPN11 c.767A>GGln256Arg+?P3.8−+−−−−−−−Live birth
15 PTPN11 c.794G>AArg265Gln−+P6.0−−−−−−−−−Live birth
16 PTPN11 c.854T>CPhe285Ser−+P8.7+++++Pericardial effusionMild pyelectasis−Lemon-shaped headToP at 23 weeks
17 PTPN11 c.854T>CPhe285Ser−+P7.7++−+Very mild−−+27 weeksLow set earsLive birth at 27 weeks, postnatal death
18 PTPN11 c.854T>CPhe285Ser++PIncreased++−−PS−+−ToP
19 PTPN11 c.922A>GAsn308Asp−+P5.5−−−−−−−−−ToP at 22 weeks
20 PTPN11 c.922A>GAsn308Asp++P13.0+−−−−−−−−ToP >20 weeks
21 PTPN11 c.922A>GAsn308Asp++P9.6+−−−−−−−−Premature delivery at 17 weeks
22 PTPN11 c.1381G>AAla461Thr−+P9.2–++++Fibrous VSDHorse shoe kidney−Malrotation bowel, ambiguous genitaliaIUFD at 17 weeks
23 PTPN11 c.1403C>TThr468Met−+P>3.5−+−−−−−−−ToP at 22 weeks
24 PTPN11 c.1403C>TThr468Met+−matP8.0−+−−−−−−−Live birth
25 PTPN11 c.1504T>GSer502Ala+?P13.7+++−−AVSDPyelectasis−Absent ductus venosus, dysmorphic facial featuresToP
26 PTPN11 c.1507G>CGly503Arg++P3.6−−−+bilat−−−−−ToP at 24 weeks
27 PTPN11 c.1530G>CGln510His++P12.0+++++Cardiomyopathy, dysplastic mitral valvePyelectasis+Brachycephaly, hepatomegaly, hypertelorism, large tongue, non-rotation bowelIUFD at 31 weeks
28 RAF1 c.770C>TSer257Leu++P8.2n/a−+−−−−−−ToP at 12 weeks
29 RAF1 c.770C>TSer257Leu++P5.5++−−−VSD−−SUAToP at 20 weeks
30 RAF1 c.770C>TSer257Leu++P6.9−−++−−−−−ToP at 19 weeks
31 RAF1 c.778A>CThr260Pro++LP6.5+−++−Hypertrophic myocardium, PS−+Echogenic bowelLive birth, postnatal death
32 RAF1 c.782C>GPro261Arg++P8.0+−−−−−−−Unilateral clubfootToP at 16 weeks
33 RIT1 c.319A>GMet107Val++PNuchal fold at 19 weeks?++++−Pyelectasis+−Died during child birth
34 RIT1 c.319A>GMet107Val+?P7.3+−−−−−−−−ToP
35 RIT1 c.319A>GMet107Val++P18.0−−+++Hypoplastic right ventricle, tricuspid atresia, pulmonary atresia, VSD−−Low set earsToP at 14 weeks
36 M AP2K1 c.383G>AGly128Asp−+LPIncreased+−++−−−−−ToP at 18 weeks
37 SHOC2 c.4A>GSer2Gly++PNuchal fold at 21 weeks+−++−Cardiomegaly, RV hypertrophy−+VentriculomegalyLive birth at 37 weeks
38 BRAF c.1391G>TGly464Val++LP11.8n/a+−−−ToF, abnormal ductus venosus, abnormal a. hepatica−−−ToP at 13 weeks
39 SOS1 c.806T>GMet269Arg++POedema around fetus−+−−−−−−Macrocephaly, SUAToP at 18 weeks
40 HRAS c.38G>AGly13Asp++P3.4++++−VSDHydronephrosis+−ToP at 24 weeks

  • AVSD, atrioventricular septum defect; DORV, double outlet right ventricle; IUFD, intrauterine fetal death; JLS, jugular lymph sacs; LP, likely pathogenic; NT, nuchal translucency; P, pathogenic; PS, pulmonary stenosis; RV, right ventricle; SUA, single umbilical artery; ToP, termination of pregnancy; VSD, ventricular septum defect; bilat, bilateral; mat, maternal; n/a, not applicable.