Table 2 Summary of diagnosed conditions and causative variants in the cohort, classified by the mode of inheritance (see Fig 0.1)

Autosomal dominant mode of inheritance (N = 41)

1

190

ATP1A3

c.2851G > A (p. Glu951Lys)

missense

41,967,732

19q13.2

1

614,820

Alternating hemiplegia of childhood 2

2

55

C19ORF12

c.204_214del (p. Gly69Argfs*10)

frameshift

29,702,957–29,702,977

19q12

1

614,298

Neurodegeneration with brain iron accumulation 4

3

147

CHD1

c.206 C > G

(p.Ser69Pro)

missense

98,904,946

5q15-q21.1

1

617,682

Pilarowski-Bjornsson syndrome

4

139

CTBP1

c.991 C > T(p.Arg331Trp)

missense

1,213,028

4p16.3

1

617,915

Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome

5

278

DEPDC5

c.1325-1G > A

splice acceptor

31,810,520

22q12.2-q12.3

1

604,364

Epilepsy, familial focal, with variable foci 1

6

14

DYRK1A

c.1294G > T

stop gained

37,505,364

21q22.13

1

614,104

Intellectual developmental disorder, autosomal dominant 7

7

101

FOXG1

c.701 C > T (p.Ser234Phe)

missense

28,767,980

14q12

2

613,454

Rett syndrome, congenital variant, FOXG1 syndrome

8

392

c.587 A > C (p.Gln196Pro)

missense

28,767,866

9

108

GABRB3

c.288G > T (p.Arg96Ser)

missense

26,621,487

15q12

2

617,113

Developmental and epileptic encephalopathy 43

10

23

c.905 A > G (p.Tyr302Cys)

missense

26,561,107

11

314

GLRA1

c.381dup (p.Phe128Leufs*11)

frame shirt

15,185,987

5q33.1

1

149,400

Hyperekplexia 1

12

161

GNB1

c.239T > C (p.Ile80Thr)

missense

1,806,503

1p36.33

1

616,973

Intellectual developmental disorder, autosomal dominant 42

13

151

KCNA2

c.997T > C (p.Phe333Leu)

missense

110,603,786

1p13.3

2

616,366

Developmental and epileptic encephalopathy 32

14

376

c.1219 C > T (p.Pro407Ser)

missense

110,603,564

15

65

KCNQ2

c.1639 C > T (p.Arg547Trp)

missense

63,413,574

20q13.33

1

613,720

Developmental and epileptic encephalopathy 7

16

237

KCNT1

c.1309 C > T (p.Leu437Phe)

missense

135,765,732

9q34.3

2

614,959

Developmental and epileptic encephalopathy 14

17

323

c.784 C > T (p.Arg262Trp)

missense

135,758,438

18

131

KDM1A

c.2410dupA

(p.Ser785Leufs*22)

frame shift

23,082,331

1p36.12

1

616,728

Cleft palate, psychomotor retardation, and distinctive facial features

19

68

KMT2C

c.8965_8970delinsAGTACCTT (p.Val2989Serfs*44)

missense

118,504,857

7q36.1

1

617,768

Kleefstra syndrome 2

20

290

KMT2D

c.14,710 C > T (p.Arg4904*)

stop gained

49,027,256

12q13.13

1

147,920

Kabuki syndrome 1

21

134

MACF1

c.7661 A > G

(p.Gln2554Arg)

missense

39,382,151

1p34.3

1

618,325

Lissencephaly 9 with complex brainstem malformation

22

44

KMT2A

c.2968_2969insAGAG (p.Cys990*)

nonsense

118,474,126

11q23.3

2

605,130

Wiedemann-Steiner syndrome

23

72

c.1038del (p.Val347fs)

frame shift

118,472,196

24

172

NPRL3

Exon 2–6 deletion

truncating

112,622 -

138,334

16p13.3

1

617,118

Epilepsy, familial focal, with variable foci 3

25

182

PAFAH1B1

c.1159 + 2T > A

splice donor

2,680,322

17p13.3

2

607,432

Lissencephaly 1

26

284

c.656G > A (p.Trp219*)

(mosaic)

nonsense

2,674,239

27

150

PTPN11

c.922 A > G

(p.Asn308Asp)

missense

112,477,719

12q24.13

1

163,950

Noonan syndrome 1

28

389

SCN1A

c.4073G > T (p.Trp1358Leu)

missense

166,002,683

2q24.3

2

607,208

Dravet syndrome

29

403

c.4265 A > G (p.Tyr1422Cys)

missense

166,002,491

30

306

SCN2A

c.2552 C > A (p.Ser851*)

nonsense

65,342,459

2q24.3

2

613,721

Developmental and epileptic encephalopathy 11

31

283

Exon 17 deletion

32

311

KCNC1

c.22G > T(p. .Glu8Ter)

missense

17,736,024

11p15.1

1

616,187

Epilepsy, progressive myoclonic 7

33

130

STXBP1

c.1606delC

127,682,459

9q34.11

2

612,164

Developmental and epileptic encephalopathy 4

34

224

c.175G > A (p.Glu59Lys)

missense

127,658,380

35

257

SYNGAP1

c.1564del (p.Glu522Lysfs*5)

frame shirt

33,438,273

6p21.32

2

612,621

Developmental disorder, autosomal Intellectual dominant 5

36

126

c.1534G > T (p.Glu512Ter)

stop gained

33,438,777

37

142

TGFBR1

c.844T > C

(p.Tyr282His)

missense

99,142,574

9q22.33

1

609,192

Loeys-Dietz syndrome 1

38

116

TLK2

c.754 C > T

(p.Gln252Ter)

stop gained

62,560,049

17q23.2

1

618,050

Intellectual developmental disorder, autosomal dominant 57

39

186

TREX1

c.341G > A (p.Arg114His)

missense

48,466,996

3p21.31

2

225,750

Aicardi-Goutieres syndrome 1

40

378

c.341G > A (p.Arg114His)

missense

48,466,996

41

145

TRRAP

c.6653 A > C (p.Glu823Ala)

missense

98,967,697

7q22.11

1

618,454

Developmental delay with or without dysmorphic facies and autism

Autosomal recessive mode of inheritance (N = 4)

42

16

ARSA

c.465 + 1G > A

splice donor

50,627,165

22q13.33

1

250,100

Metachromatic leukodystrophy

c.542T > G (p.Ile181Ser)

stop gained

50,626,976

43

180

FBXL4

c.45T > G (p.Tyr15*)

c.627_633del (p.Asn210Leufs*9)

frame shift

98,926,944

6q16.1-16.2

1

615,471

Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type)

44

56

NPC1

c.2861 C > T (p.Ser954Leu)

missense

23,539,405

18q11.2

1

257,220

Niemann-Pick disease, type C1

c.1026G > A (p.Trp342*)

nonsense

23,556,543

45

332

PAH

c.1222 C > T (p.Arg408Trp)

missense

102,840,493

12q23.2

1

261,600

Phenylketonuria

c.473G > A (p.Arg158Gln)

missense

102,866,632

X-linked dominant (N = 9)

46

42

CDKL5

c.372_385del (p.His124Glnfs*2)

frame shift

18,579,937

Xp22.13

1

300,672

Developmental and epileptic encephalopathy 2

47

251

MECP2

c.397 C > T (p.Arg133Cys)

missense

154,031,431

Xq28

5

312,750

Rett syndrome

48

83

c.806del (p.Gly269Alafs*20)

frame shift

154,031,025

49

414

c.1084_1216del (p.Pro362Argfs*3)

frame shift

154,030,743

50

106

c.844del (p.Arg282fs)

frame shift

154,031,020

51

95

c.1115 C > A (p.Ser372Ter)

stop gained

154,030,749

52

157

SLC35A2

c.845G > A

(p.Gly221Glu)

missense

48,905,064

Xp11.23

1

300,896

Congenital disorder of glycosylation, type IIm

53

60

WDR45

c.1013_1014del (p.Phe338Tyrfs*3)

frame shift

49,074,874

Xp11.23

2

300,894

Neurodegeneration with brain iron accumulation 5

54

61

c.64del (p.Cys22Alafs*16)

frame shift

49,077,902

X-linked recessive (N = 2)

55

400

ATP7A

c.2938 C > T (p.Arg980Ter)

stop gained

78,029,271

Xq21.1

1

309,400

Menkes disease

56

200

ARX

c.1058 C > T (p.Pro353Leu)

missense

25,012,937

Xp21.3

1

308,350

Developmental and epileptic encephalopathy 1