Skip to main content

Table 2 Overview of cases with positive findings explanatory of the fetal phenotypes

From: Whole-exome sequencing in deceased fetuses with ultrasound anomalies: a retrospective analysis

Case No

GA (weeks)

Ultrasound finding(Hpo number)

Gene(OMIM)

Variant

Variant classification (ACMG criteria)

Inheritance mode

Disease

Origin

1

24

Polycystic kidney dysplasia (0,000,113)

PKHD1(263,200)

NM_138694:c.8301delC(p.Asn2768fs) het

Exons 58–60 repeat het

LP(PVS1 + PM2)

LP

AR

Polycystic Kidney Disease 4 With Or Without Polycystic Liver Disease

Maternal/paternal

2

24

Polycystic kidney dysplasia

(0,000,113)

Oligohydramnios (0,001,562)

JAG1(118,450)

NM_000214:c.2078_2079delGT(p.Cys693fs) het

P(PVS1 + PM2 + PP5)

AD

Alagille Syndrome 1

Maternal

3

14+3

Abnormality of long bone morphology (0,011,314)

Medial deviation of the foot

(0,008,082)

Hydrops fetalis (0,001,789)

COL1A1(114,000)

NM_000088:c.2399G > A(p.Gly800Glu) het

LP(PM1 + PM2 + PM6 + PP2 + PP3)

AD

Caffey disease

De novo

4

18+6

Abnormal thorax morphology

(0,000,765)

Aplasia/hypoplasia of the extremities (0,009,815)

Thickened nuchal skin fold

(0,000,474)

FGFR3

(100,800)

NM_000142:c.742C > T(p.Arg248Cys) het

P(PS4 + PM1 + PM2 + PP3)

AD

Achondroplasia

De novo

5

19

Short lower limbs (0,006,385)

FGFR3

(100,800)

NM_000142:c.742C > T(p.Arg248Cys) het

P(PM1 + PM2 + PP3 + PS4)

AD

Achondroplasia

De novo

6

24+1

Aplasia/hypoplasia of the extremities (0,009,815)

Abnormal thorax morphology

(0,000,765)

FGFR3

(100,800)

NM_000142:c.742C > T(p.Arg248Cys) het

P(PM1 + PM2 + PP3 + PS4)

AD

Achondroplasia

De novo

7

33+1

Abnormal thorax morphology

(0,000,765)

Aplasia/hypoplasia of the extremities (0,009,815)

DYNC2H1

(613,091)

NM_001080463:c.9182_9185delAGAG(p.Glu3061fs) het

c.7495C > G(p.Leu2499Val) het

LP(PVS1 + PM2_S)

VUS(PM1 + PM2_S + PM3)

AR

Asphyxiating Thoracic Dystrophy 3

Maternal/paternal

8

13

Micrognathia (0,000,347)

GNAI3

(602,483)

NM_006496:c.119G > T(c.119G > T) het

LP(PM1 + PM2 + PM6 + PP3)

AD

Auriculocondylar Syndrome 1

De novo

9

24

Hydrocephalus (0,000,238)

LICAM

(307,000)

NM_000425:c.1258delT(p.Tyr420fs)

LP(PVS1 + PM2_S)

XR

Hydrocephalus Due To Congenital Stenosis Of Aqueduct Of Sylvius

Maternal

10

29+4

Polycystic kidney dysplasia

(0,000,113)

Polyhydramnios (0,001,561)

PKHD1

(263,200)

NM_138694:c.979A > G(p.Asn327Asp) het

c.11282C > A(p.Gln3761Lys) het

VUS(PM1 + PM2)

VUS(PM2 + PP3)

AR

Polycystic Kidney Disease 4 With Or Without Polycystic Liver Disease

Maternal/paternal

11

16

Short long bone (0,003,026)

COL1A1

(166,200)

NM_000088:c.1273G > A(p.Gly425Ser) het

LP(PM1 + PM2_S + PM6 + PP2 + PP3)

AD

Osteogenesis Imperfecta, Type I

De novo

12

23

Hyperechogenic kidneys

(0,004,719)

ACE

(267,430)

NM_000789:c.1028G > A(p.Trp343*) hom

P(PVS1 + PM2_S + PM3)

AR

Renal Tubular Dysgenesis

Maternal/paternal

13

17+3

Aplasia/hypoplasia of the extremities (0,009,815)

Abnormal thorax morphology

(0,000,765)

Polydactyly (0,010,442)

DYNC2H1

(613,091)

NM_001080463:c.557G > T(p.Gly186Val) het

c.7643 T > C(p.Phe2548Ser) het

VUS(PM2 + PM3)

LP(PS1 + PM2 + PM3)

AR

Asphyxiating Thoracic Dystrophy 3

Maternal/paternal

14

14+

Short long bone (0,003,026)

Abnormal thorax morphology

(0,000,765)

Hypoplasia of the frontal bone

(0,005,466)

Large fontanelles (0,000,239)

DYNC2H1

(613,091)

NM_001080463:c.8190G > T(p.Leu2730Phe) het

c.8621delC(p.Leu2876fs*15) het

LP(PVS1 + PM2)

LP(PVS1 + PM2)

AR

Asphyxiating Thoracic Dystrophy 3

Maternal/paternal

15

25+

Hydrocephalus (0,000,238)

Dilation of lateral ventricles

(0,006,956)

Absent septum pellucidum

(0,001,331)

L1CAM

(307,000)

NM_000425:c.1989C > G(p.Tyr663*) hemi

LP(PVS1 + PM2)

XR

Hydrocephalus Due To Congenital Stenosis Of Aqueduct Of Sylvius

Maternal

16

21+2

Abnormal thorax morphology

(0,000,765)

Aplasia/hypoplasia of the extremities (00,098,150)

DYNC2H1

(613,091)

NM_001080463:c.2070A > T(p.Arg690Ser) het

c.8946 + 1G > A het

VUS(PM2_S + PM3)

LP(PVS1 + PM2)

AR

Asphyxiating Thoracic Dystrophy 3

Maternal/paternal

17

23

Medial deviation of the foot

(0,008,082)

Abnormal hand morphology

(0,005,922)

NEB

(619,334)

NM_001271208:c.25159C > T(p.Gln8387*) het

c.7494dupT(p.Asp2499fs) het

LP(PVS1 + PM2_S + PP4)

LP(PVS1 + PM2_S + PP4)

AR

Arthrogryposis Multiplex Congenita 6

Maternal/paternal

18

12+4

Aplasia/Hypoplasia of the radius (0,006,501)

SALL4

(607,323)

NM_001318031:c.844delC(p.Gln282fs) het

P(PVS1 + PM2 + PP1)

AD

Duane-radial ray syndrome

Paternal

19

19+4

Hydronephrosis (0,000,126)

Abnormality of bladder morphology (0,025,487)

Rocker bottom foot (0,001,838)

CAD

(616,457)

NM_001306079:c.2665_2666insCG(p.Lys889fs) het

c.6055G > A(p.Asp2019Asn) het

LP(PVS1 + PM2)

VUS(PM2 + PP2 + PP3)

AR

Epileptic Encephalopathy, Early Infantile, 50

Maternal/paternal

20

23

Skeletal dysplasia (0,002,652)

Abnormality of cardiovascular system morphology(0,030,680)

Renal hypoplasia (0,000,089)

NOTCH2

(610,205)

NM_024408:c.6973C > T(p.Gln2325*)

P(PVS1 + PS2 + PM2_S)

AD

Alagille Syndrome 2

De novo

21

24

Talipes equinovarus

(0,001,762)

ECEL1

(615,065)

NM_004826:c.1700C > G(p.Pro567Arg) het

c.922C > T(p.Gln308*)

VUS(PM3 + PM2_S + PP3)

LP(PVS1 + PM2_S)

AR

Arthrogryposis, Distal, Type 5d

Maternal/paternal

22

26

Stillbirth (0,003,826)

PLAA

(617,527)

NM_001031689:c.1658-2A > G het

c.1043delC(p.Thr348fs) het

LP(PVS1 + PM2_S + PP3)

LP(PVS1 + PM2_S)

AR

Neurodevelopmental Disorder With Progressive Microcephaly, Spasticity, And Brain Anomalies

Maternal/paternal

23

18

Abnormal lower limb bone morphology

(0,040,069)

COL1A1

(114,000)

NM_000088:c.3150_3158dupTCCTGGTGC(p.Ala1053_Pro1054insProGlyAla) het

LP(PM2_S + PM4 + PM6)

AD

Caffey disease

De novo

24

25

Polycystic kidney dysplasia

(0,000,113)

PKHD1

(263,200)

NM_138694:c.3305_3306delAT(p.Tyr1102fs) het

c.5935G > A(p.Gly1979Arg) het

P(PVS1 + PM2_S + PP4)

LP(PM3 + PM2_S + PM1 + PP3 + PP4)

AR

Polycystic Kidney Disease 4 With Or Without Polycystic Liver Disease

Maternal/paternal

25

24

Cleft upper lip (0,000,204)

Cleft palate (0,000,175)

TFAP2A

(113,620)

NM_001372066:c.890-1G > A

P(PVS1 + PM2)

AD

Branchiooculofacial Syndrome

De novo

26

13+3

Cleft upper lip (0,000,204)

Cleft palate (0,000,175)

KAT6B

(606,170)

NM_001372066:c.4017delA(p.Gly1340fs) het

LP(PVS1 + PM2_S + PM6)

AD

Genitopatellar syndrome

De novo

27

24

Abnormal heart morphology

(0,001,627)

ARID1A

(614,607)

NM_006015:c.2402dupG(p.Gln802fs) het

LP(PVS1 + PM2)

AD

Coffin-siris Syndrome 2

De novo

28

19

Pleural effusion (0,002,202)

Fetal choroid plexus cysts

(0,011,426)

PIEZO1

(616,843)

NM_001142864:c.5262delG(p.Trp1754fs) het

c.1684C > T(p.Gln562*) het

P(PVS1 + PM2_S + PM3)

LP(PVS1 + PM2)

AR

Lymphedema, Hereditary, Iii

Maternal/paternal

  1. GA, Gestational age; HPO, Human Phenotype Ontology, pathogenic; LP, Likely pathogenic; VUS, Variant of unknown significance; PM2_S, PM2_supporting; AR, Autosomal recessive; AD, Autosomal dominant; XLR, X-linked recessive; het, heterozygous variant; hemi, hemizygous variant; hom, homozygous variant