Table 2 Clinical findings and summary of pathogenic variants identified by WES or WGS

Group (i)

Familial cases several generations

Patient_1

M

ID

DYNC1H1

NM_001376.5

c.4462dupC; p.Arg1488Profs*5

AD (mat)

ID, autosomal dominant 13 (#614,563)

Patient_2

M

ID, microcephaly, dysmorphism

VPS13B

NM_017890.4

c.5998_5999delCT; p.Leu2000Alafs*2 (mat)

c.10475_10476delAA; p.Lys3492Argfs*19 (pat)

AR

Cohen syndrome (#216,550)

[13]

Patient_3

M

ID

IQSEC2

NG_021296.1

c.3116-3_3116-2delCA

X-linked (mat)

ID, X-linked 1/78 (#309,530)

[14]

Patient_4

M

ID

SMC1A

NM_006306.2

c.1405C > T; p.Arg469Cys

X-linked (mat)

Cornelia de Lange syndrome 2 (#300,590)

[13]

Patient_5

M

ID

OCRL

NM_000276.3

c.1567G > A; p.Asp523Asn

X-linked (mat)

Dent disease (#300,555)

[13]

Patient_6

F

ID

UBE3A

NM_130839.4

c.2009delA; p.Asp671Metfs*3

Imprinting (mat)

Angelman syndrome (#105,830)

Group (ii)

Sibling couple

Patient_7

M

ID, DD, GR

PYCR1

NM_001282280.1

c.797 + 2delTGGG

AR

Cutis laxa type IIB (#612,940)

Patient_8

M

Severe ID, ASD

THOC2

NM_001081550.1

c.3323C > T; p.Ser1108Leu

X-linked (germline mosaicism)

ID, X-linked 12/35 (#300,957)

[11]

Patient_9

M

ID, SD

CLCN4

NM_001830.4

c.758 G > A; p.Arg253Gln

X-linked (mat)

Raynaud-claes syndrome (#300,114)

Group (iii)

Trios

Patient_10

M

ASD, no speech development

CHD9

NM_001308319

c.3772A > C; p.Thr1258Pro

AD (de novo)

Patient_11

F

Severe ID, DD and PDD, myoclonic seizures

DHDDS

NM_024887.3

c.632G > A; p.Arg211Gln

AD (de novo)

DD and seizures with or without movement abnormalities (# 617,836)

Patient_12

M

ID, DD

PHIP

NM_017934.7

c. 5317 C > T; p.Arg1773Ter

AD (de novo)

DD, ID obesity, dysmorphic features (#617,991)

Patient_13

M

Moderate ID, epilepsy, neonatal hypotonia, obesity, SD, BHD

SETD1B

NM_001353345.1

c. 3772 C > T; p.Arg1258Ter

AD (de novo)

ID with seizures and language delay (#619,000)

[12]

Patient_14

F

Microcephaly

TUBB5

NM_001293213.2

c.1201 G > A; p.Glu401Lys

AD (de novo)

Cortical dysplasia, complex, with other brain malformations 6 (#615,771)

[15]

Patient_15

M

ID

ACSL4

NM_022977.2

c.1030T > C; p.Ser344Pro

X-linked (mat)

ID, X-linked 63 (#300,387)

Patient_16

M

ID, severe SD, infantile hypotonia

THOC2

NM_001081550.1

c.3361A > G; p.Arg1121Gly

X-linked (mat)

ID, X-linked 12/35 (#300,957)

[11]

Patient_17

M

Moderate ID, macrocephaly

GRIA3

NM_000828.4

c.1892G > A; p.Arg631His

X-linked (mat)

ID, X-linked 94 (#300,699)

Group (iv)

Sporadic cases

Patient_18

F

BHD, LD, bilateral hearing loss, cardiac malformation

ANKRD11

NM_013275.5

c.1940_1941delinsT; p. Arg647Leufs*6

AD (de novo)

KBG syndrome (#148,050)

Patient_19

M

ID, BHD

ADNP

NM_015339.4

c.1792C > T; p.Gln598Ter

AD (de novo)

Helsmoortel-van der Aa syndrome (#615,873)

Patient_20

M

GR, ID, compatible with Cornelia de Lange

NIPBL

NM_133433.4

c.385T > C; p.Ser129Pro

AD (de novo)

Cornelia de Lange syndrome 1 (#122,470)

Patient_21

F

ID, GR, facial dysmorphism, compatible with Cornelia de Lange

NIPBL

NM_133433.4

c.5329-15A > G

AD (de novo)

Cornelia de Lange syndrome 1 (#122,470)

Patient_22

F

ID, DD

NSD1

NM_022455.4

c.2276C > G; p.Ser759Ter

AD (de novo)

Sotos syndrome 1 (#117,550)

Patient_23

F

PDD, macrocephaly, hypotonia

CSPP1

NM_024790.6

c.363_367delTAAAT; p.Leu123Rfs*19 (pat)

c.2243_2244delAA; p.Glu750Gfs*30 (mat)

AR

Joubert syndrome 21 (#615,636)

Patient_24

M

PDD

EMC1

NM_015047.2

c.797T > G; p.Leu266Ter (mat)

c.285 T > C; p.Phe953Ser (pat)

AR

Cerebellar atrophy, visual impairment, and PDD (#616,875)

Patient_25

F

ID, DD, microcephaly, hypotonia

DDX3X

NM_001356.3

c.1415A > G; p.His472Arg

X-linked (de novo)

ID, X-linked 102 (#300,958)

Patient_26

M

Phenotype compatible with Opitz syndrome

MID1

NM_0000381.3

c.602_605del; p.Val201GlyfsTer11

X-linked*

Opitz GBBB syndrome, type I (#300,000)

Patient_27

F

Dysmorphic features and LD

PPP2R5D

NM_006245.3

c.592G > A; p.Glu198Lys

AD (de novo)

Mental retardation, autosomal dominant 35 (#616,355)

Patient_28

M

ASD, ID

WAC

NM_016628.5

c.1280_1281delCTinsGAG

AD (de novo)

Desanto-Shinawi syndrome (#616,708)

Patient_29

M

ID and dysmorphic features

KCNT2

NM_198503.5

c.569G > A; p.Arg190His

AD (de novo)

Developmental and epileptic encephalopathy 57 (#617,771)

[20, 21]

Patient_30

F

ID, absent speech, dysmorphic features

CNOT3

NM_014516.3

c.169C > T (p.Arg57Trp)

AD (de novo)

Intellectual developmental disorder with speech delay,

autism, and dysmorphic facies

Group (v)

Whole genome sequencing

Patient_31

M

Severe ID, absent speech, BHD

TRAPPC9

NM_031466.7

c.1037G > A; p.Gly346Glu (mat)

arr8q24(141382973_141473138) × 1 (pat)

AR

ID, autosomal recessive 13 (#613,192)

[10]