Table 2 The 27 genes firstly reported in prenatal cases

4

Female

Agenesis of corpus callosum, ventriculomegaly

NFIA(600727)

NM_001145512.1

c.1112C>A^b

p.(Ser371Ter)

Nonsense

Het

P

PVS1, PS2, PM2

De novo

AD

BRAIN MALFORMATIONS WITH OR WITHOUT URINARY TRACT DEFECTS(613735)

Matching HPO entry: Agenesis of corpus callosum, Ventriculomegaly

─

19

Male

Increased nuchal translucency, agenesis of corpus callosum, ventriculomegaly

NFIA(600727)

NM_001145512.1

c.483A>C^b

p.(Arg161Ser)

Missense

Het

LP

PS2, PM1, PM2, PP3

De novo

AD

BRAIN MALFORMATIONS WITH OR WITHOUT URINARY TRACT DEFECTS(613735)

Matching HPO entry: Agenesis of corpus callosum, Ventriculomegaly

Increased nuchal translucency

7

Male

Widened posterior fossa

EZH2(601573)

NM_004456.4

c.2050C>T

p.(Arg684Cys)

Missense

Het

P

PS2, PS3_PM, PS4_PP, PM2, PM5, PP3

De novo

AD

WEAVER SYNDROME(277590)

Matching central nervous system

Widened posterior fossa

108

Male

Hypoplasia of the ulna, radial dysplasia, abnormality of digit

EZH2(601573)

NM_004456.4

c.47G>A^b

p.(Arg16Gln)

Missense

Het

LP

PS2_PM, PM1_PP, PM2, PP3

De novo

AD

WEAVER SYNDROME(277590)

Matching HPO entry: Abnormality of digit

Hypoplasia of the ulna, Radial dysplasia

12

Female

Hypoplasia of the corpus callosum, ventriculomegaly

PPP2R1A(605983)

NM_014225.5

c.775G>A

p.(Val259Ile)

Missense

Het

LP

PS2, PM2, PP3

De novo

AD

MENTAL RETARDATION, AUTOSOMAL DOMINANT 36; MRD36(616362)

Matching HPO entry: Hypoplasia of the corpus callosum, Ventriculomegaly

─

30

Male

Hydrocephalus, hypoplasia of the corpus callosum

PPP2R1A(605983)

NM_014225.5

c.544C>T

p.(Arg182Trp)

Missense

Het

P

PM1, PM2, PS3_PP, PS2_PVS

De novo

AD

MENTAL RETARDATION, AUTOSOMAL DOMINANT 36 (616362)

Matching HPO entry: Hydrocephalus, Hypoplasia of the corpus callosum

─

21

Male

Increased nuchal translucency, ventriculomegaly

ADNP(611386)

NM_015339.4

c.2161C>T^b

p.(Gln721Ter)

Nonsense

Het

LP

PVS1_PS, PS2_PM, PM2

De novo

AD

HELSMOORTEL-VAN DER AA SYNDROME(615873)

Matching HPO entry: Ventriculomegaly

Increased nuchal translucency

46

Male

Tetralogy of Fallot

ADNP(611386)

NM_015339.4

c.2156dupA

p.(Tyr719Ter)

Frameshift

Het

P

PVS1_PS, PS2, PM2

De novo

AD

HELSMOORTEL-VAN DER AA SYNDROME(615873)

Matching cardiovascular system

─

18

Female

Dilation of lateral ventricles, polyhydramnios

ARV1(611647) ^a

NM_022786.3

c.409delG^b

p.(Glu137AsnfsTer13)

Frameshift

Het

P

PVS1, PM2, PM3

Pat

AR

EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 38 (617020)

Matching central nervous system

Dilation of lateral ventricles, Polyhydramnios

NM_022786.3

c.518dupA

p.(Pro174AlafsTer14)

Frameshift

Het

P

PVS1, PM2_PP, PM3

Mat

31

Male

Bilateral choroid plexus cyst, single umbilical artery

ZMYM2(602221) ^a

NM_003453.4

c.534dupA^b

p.(Asp179ArgfsTer3)

Frameshift

Het

P

PVS1, PS2_PP, PM2

De novo

AD

Neurodevelopmental craniofacial syndrome with variable renal and cardiac abnormalities(619522)

Matching central nervous system

Bilateral choroid plexus cyst, Single umbilical artery

38

Male

Micrognathia, cleft palate

KCNK9(605874)

NM_001282534.1

c.706G>C

p.(Gly236Arg)

Missense

Het

P

PS2_PVS, PS3_PP, PM2

De novo

AD

BIRK-BAREL SYNDROME(612292)

Matching HPO entry: Micrognathia, Cleft palate

─

40

Male

Congenital cataract

CRYAA(123580)

NM_000394.3

c.34C>T

p.(Arg12Cys)

Missense

Het

P

PS4, PM2, PP1_PS, PP3

Pat(affected)

AD

CATARACT 9, MULTIPLE TYPES; CTRCT9(604219)

Matching HPO entry: Congenital cataract

─

65

Female

Transposition of the great arteries

MAPK1(176948) ^a

NM_002745.4

c.1061T>G

p.(Phe354Cys)

Missense

Het

LP

PS2, PM2, PP3, PP2

De novo

AD

Noonan syndrome 13 (619087)

Matching cardiovascular system

─

102

Male

Short long bone, wind-swept deformity of the knees

GDF5(601146)

NM_000557.5

c.1335T>G

p.(Asn445Lys)

Missense

Het

P

PS2_PM, PM1_PP, PM2, PP3

De novo

AD

MULTIPLE SYNOSTOSES SYNDROME 2 (610017)

Matching HPO entry: Short long bone

─

107

Male

Redundant neck skin, abnormal posturing, flexion contracture

SCN4A(603967)

NM_000334.4

c.3502delC^b

p.(Leu1168SerfsTer5)

Frameshift

Het

LP

PVS1, PM2

Mat

AR

MYASTHENIC SYNDROME, CONGENITAL, 16 (614198)

Matching HPO entry: Flexion contracture

─

NM_000334.4

c.3395G>C^b

p.(Arg1132Pro)

Missense

Het

LP

PM2, PM3_PP, PM5, PP3

De novo

110

Female

Abnormality of the middle and the distal phalanx of the 3rd finger, abnormality of the index finger, split foot

PUF60(604819)

NM_078480.2

c.24+3A>T^b

-

Splice region

Het

LP

PVS1_PM, PS2_PM, PM2

De novo

AD

VERHEIJ SYNDROME(615583)

Matching skeletal system

Split foot

114

Female

Talipes equinovarus, abnormality of the hand

ZC4H2(300897)

NM_018684.3

c.562-1G>T^b

-

Splice acceptor

Het

P

PVS1_PS, PS2

De novo

XL

WIEACKER-WOLFF SYNDROME, FEMALE-RESTRICTED(301041)

Matching HPO entry: Talipes equinovarus, Abnormality of the hand

─

116

Female

Short long bone

SMAD4(600993)

NM_005359.5

c.1498A>G

p.(Ile500Val)

Missense

Het

P

PS2, PS4, PM2_PP, PM5, PP3

De novo

AD

MYHRE SYNDROME(139210)

Matching HPO entry: Short long bone

─

118

Female

Talipes equinovarus, hand clenching

TPM2(190990)

NM_003289.4

c.463G>A

p.(Ala155Thr)

Missense

Het

LP

PS3_PP, PS4_PM, PM2, PP3

Mat (affected)

AD

ARTHROGRYPOSIS, DISTAL, TYPE 1A(108120)

Matching HPO entry: Talipes equinovarus, Hand clenching

─

159

Female

Talipes equinovarus

BRPF1(602410)

NM_001003694.1

c.1723-1G>C^b

-

Splice acceptor

Het

P

PS2, PM2, PVS1_PS

De novo

AD

INTELLECTUAL DEVELOPMENTAL DISORDER WITH DYSMORPHIC FACIES AND PTOSIS (617333)

Matching HPO entry: Talipes equinovarus

─

163

Male

Intrauterine growth retardation

KAT6A(601408)

NM_006766.4

c.751C>T^b

p.(Arg251Ter)

Nonsense

Het

P

PVS1, PS2, PM2

De novo

AD

ARBOLEDA-THAM SYNDROME(616268)

Matching HPO entry: Intrauterine growth retardation

─

169

Male

Increased nuchal translucency

KMT2C(606833)

NM_170606.2

c.12906delT^b

p.(Ala4303ProfsTer23)

Frameshift

Het

P

PVS1, PS2, PM2

De novo

AD

KLEEFSTRA SYNDROME 2 (261652)

Not reported previously. Homologous genes KMT2A/KMT2D matching HPO entry: Increased nuchal translucency

Increased nuchal translucency

170

Male

Increased nuchal translucency, bilateral choroid plexus cysts

KCNT1(608167)

NM_020822.2

c.1420C>T

p.(Arg474Cys)

Missense

Het

P

PM2, PP3, PS2_PVS

De novo

AD

DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 14 (614959)

Not reported previously

Increased nuchal translucency, Bilateral choroid plexus cysts

172

Female

Increased nuchal translucency, cystic hygroma

NFIB(600728)

NM_001190737.1

c.376A>G

p.(Lys126Glu)

Missense

Het

LP

PM1, PP3, PS3_PP, PS2_PP, PM2

De novo

AD

MACROCEPHALY, ACQUIRED, WITH IMPAIRED INTELLECTUAL DEVELOPMENT(618286)

Not reported previously

Increased nuchal translucency, cystic hygroma

189

Male

Micrognathia, arthrogryposis multiplex congenita, FGR

UBA1(314370)

NM_153280.2

c.1617G>T

p.(Met539Ile)

Missense

Hemi

LP

PM1, PM2, PP3, PP4

Mat

XR

SPINAL MUSCULAR ATROPHY, X-LINKED 2 (301830)

Matching HPO entry: Micrognathia, Arthrogryposis multiplex congenita

─

206

Female

Increased nuchal translucency, abnormality of the hand, intracranial hemorrhage, widened posterior fossa, porencephalic cyst

PLOD3(603066)

NM_001084.4

c.1890T>G

p.(Tyr630Ter)

Nonsense

Het

LP

PVS1,PM2

Mat

AR

BONE FRAGILITY WITH CONTRACTURES, ARTERIAL RUPTURE, AND DEAFNESS(612394)

Matching HPO entry: Abnormality of the hand, Intracranial hemorrhage

Increased nuchal translucency, Widened posterior fossa, Porencephalic cyst

NM_001084.4

c.1354C>T

p.(Arg452Ter)

Nonsense

Het

LP

PVS1,PM2

Pat

218

Female

Ventriculomegaly, Tetralogy of Fallot, right aortic arch

MTOR(601231)

NM_004958.3

c.7255G>A

p.(Glu2419Lys)

Missense

Het

P

PS2, PM2, PP3, PP2

De novo

AD

SMITH-KINGSMORE SYNDROME(616638)

Matching HPO entry: Ventriculomegaly

Tetralogy of Fallot, Right aortic arch

219

Male

Polyhydramnios, short long bone, cardiomegaly

KMT2A(159555)

NM_001197104.1

c.4219-1G>A^b

-

Splice acceptor

Het

P

PM2, PVS1, PS2_PM

De novo

AD

WIEDEMANN-STEINER SYNDROME(605130)

Matching HPO entry: Short long bone

Polyhydramnios, Cardiomegaly

221

Male

Aplasia of the nasal bone, abnormality of ductus venosus blood flow, single umbilical artery, ventriculomegaly, Dandy-Walker malformation, congenital diaphragmatic hernia

ARID1A(603024)

NM_006015.4

c.5853dupC^b

p.(Ile1952HisfsTer11)

Frameshift

Het

P

PS2, PM2, PVS1_PS

De novo

AD

COFFIN-SIRIS SYNDROME 2 (614607)

Matching HPO entry: Ventriculomegaly, Dandy-Walker malformation

─

225

Male

Supraventricular tachycardia, enlarged cisterna magna, ascites, pleural effusion, polyhydramnios

CSNK2A1(115440)

NM_001895.3

c.838C>T^b

p.(Arg280Ter)

Nonsense

Het

LP

PVS1_PS, PM1, PM2

De novo

AD

OKUR-CHUNG NEURODEVELOPMENTAL SYNDROME(617062)

Matching cardiovascular system; PMID: 29568000

Supraventricular tachycardia, Pleural effusion, Polyhydramnios

229

Male

Large for gestational age, polyhydramnios

CLCN5(300008) ^a

NM_001127898.3

c.934-1G>T^b

-

Splice acceptor

Hemi

LP

PVS1_PS, PM1, PM2

Mat

XR

DENT DISEASE 1 (300009)

PMID: 18540256, 27174143

─