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Table 1 The cardiac manifestations and mutation profiles of 47 pediatric patients with RASopathy and HCM

From: Clinical and mutation profile of pediatric patients with RASopathy-associated hypertrophic cardiomyopathy: results from a Chinese cohort

Case

Sex

Age HCM Diagnosed (months)

Clinical phenotype

LVOTO

Associated cardiac defect

Gene Mutation

Origin of mutation

ACMG classification

Follow-up time (years)

01

M

1.7

NSML

+

ASD

PTPN11, c.836A > G (p.Y279C)

De novo

Pathogenic

7.1

02

M

12

NSML

+

–

PTPN11, c.836A > G (p.Y279C)

De novo

Pathogenic

15.2

03

M

1.0

NSML

–

PVS

PTPN11, c.836A > G (p.Y279C)

De novo

Pathogenic

1.4

04

F

2 d

NS

+

–

PTPN11, c.836A > G (p.Y279C)

De novo

Pathogenic

1.2

05

M

6.0

NS

–

–

PTPN11, c.836A > G (p.Y279C)

De novo

Pathogenic

0.5

06

F

10

NS

–

ASD, PVS

PTPN11, c.854 T > C (p.F285S)

De novo

Pathogenic

1.6

07

M

3 d

–

–

ASD

PTPN11, c.1391G > C (p.G464A)

De novo

Pathogenic

2.0

08

M

10

NS

+

–

PTPN11, c.1492C > T (p.R498W)

Mother

Pathogenic

6.8

09

M

Fetal

NS

+

ASD, PVS

PTPN11, c.1517A > C (p.Q506P)

De novo

Pathogenic

4.0

10

F

8 d

NS

–

ASD, PDA

PTPN11, c.1517A > C (p.Q506P)

De novo

Pathogenic

1.6

11

M

17 d

NS

–

ASD, PVS

PTPN11, c.1517A > C (p.Q506P)

De novo

Pathogenic

Die at 6.0 ms old

12

F

Fetal

NS

+

–

PTPN11, c.1528C > G (p.Q510E)

De novo

Pathogenic

4.9

13

F

2.5

–

+

ASD

PTPN11, c.1528C > G (p.Q510E)

De novo

Pathogenic

Die at 3.0 ms old

14

M

1.0

NS

+

–

PTPN11, c.1528C > G (p.Q510E)

De novo

Pathogenic

8.3

15

F

1.5

NS

+

PVS

PTPN11, c.1528C > G (p.Q510E)

De novo

Pathogenic

3.9

16

M

1 d

NS

+

VSD

PTPN11, c.1528C > G (p.Q510E)

De novo

Pathogenic

0.7

17

M

1 d

NS

+

VSD

PTPN11, c.1528C > G (p.Q510E)

De novo

Pathogenic

Die at 3.5 ms old

18

M

3 d

NS

+

–

PTPN11, c.1528C > G (p.Q510E)

De novo

Pathogenic

2.0

19

F

1.3

NS

+

–

PTPN11, c.1528C > G (p.Q510E)

De novo

Pathogenic

9.3

20

F

9.0

NS

+

ASD, PVS

RAF1, c.770C > T (p.S257 L)

De novo

Pathogenic

3.9

21

F

8.0

NSML

+

–

RAF1, c.770C > T (p.S257 L)

De novo

Pathogenic

13.1

22

M

12

NS

–

VSD, ASD

RAF1, c.770C > T (p.S257 L)

De novo

Pathogenic

1.8

23

M

2 d

NS

–

ASD

RAF1, c.770C > T (p.S257 L)

De novo

Pathogenic

1.1

24

F

30

NS

–

ASD

RAF1, c.770C > T (p.S257 L)

De novo

Pathogenic

6.5

25

M

6.0

NS

+

ASD, PVS

RAF1, c.770C > T (p.S257 L)

De novo

Pathogenic

1.2

26

F

4.0

NS

–

DORV, VSD, ASD, PVS

RAF1, c.781C > A (p.P261T)

De novo

Pathogenic

3.6

27

F

5.5

NS

–

–

RAF1 c.786 T > G (p.N262K) a

De novo

Pathogenic

7.4

28

F

12

NS

+

ASD

RAF1 , c.788 T > G (p.V263G) a

De novo

Pathogenic

1.1

29

M

17

NS

+

–

RAF1, c.1472C > T (p.T491I)

NA

Pathogenic

1.3

30

M

8.1y

NS

–

ASD

RAF1,c.1837C > G (p.L613 V)

De novo

Pathogenic

3.7

31

F

16 d

NS

–

ASD, PVS

KRAS, c.101C > T (p.P34L)

De novo

Pathogenic

0.9

32

M

34

NS

–

ASD, LSVC

KRAS, c.178G > A (p.G60S)

De novo

Pathogenic

2.0

33

M

2.0

NS

–

–

KRAS, c.458A > T (p.D153V)

De novo

Pathogenic

3.0

34

M

15 d

NS

–

ASD, PDA

KRAS, c.458A > T (p.D153V)

De novo

Pathogenic

0.9

35

F

16

NS

–

ASD, PVS

KRAS, c.458A > T (p.D153V)

De novo

Pathogenic

0.8

36

F

3.0

NS

–

ASD, PVS

RIT1, c.170C > G (p.A57G)

De novo

Pathogenic

0.9

37

F

17

NS

–

ASD, PVS, PDA

RIT1, c.170C > G (p.A57G)

De novo

Pathogenic

1.4

38

F

6.8

NS

–

ASD, PVS,VSD

RIT1, c.170C > G (p.A57G)

De novo

Pathogenic

4.0

39

M

2.4

NS

–

ASD, PVS

RIT1, c.270G > C (p.M90I)

De novo

Pathogenic

4.2

40

M

3.5

CFCS

–

–

BRAF, c.770A > G (p.Q257R)

De novo

Pathogenic

0.9

41

F

5.0

CFCS

–

ASD, PVS

BRAF, c.1502A > G (p.E501G)

De novo

Pathogenic

0.6

42

F

5.0

CFCS

–

VSD

BRAF , c.1796C > T (p.T599I) a

De novo

Pathogenic

3.7

43

M

6.0y

NS

+

–

SOS1 c.1644 T > G (p.S548R)

De novo

Pathogenic

7.4

44

M

3.0

NS

+

ASD

SOS1, c.2536G > A (p.E846K)

De novo

Pathogenic

17.1

45

M

3.0

CS

–

ASD, PVS

HRAS, c.179G > A (p.G60D)

De novo

Pathogenic

3.8

46

M

3.0

NS/LAH

–

–

SHOC2, c.4A > G (p.S2G)

De novo

Pathogenic

2.7

47

M

1.0

NS

+

ASD

LZTR1 , c.509G > C(p.R170P) a LZTR1 , c.2374 T > G(p.C792G) a

Mother

Father

Likely pathogenic

Likely pathogenic

4.2

  1. HCM hypertrophic cardiomyopathy, LVOTO left ventricular outflow tract obstruction, ACMG American College of Medical Genetics and Genomics, NSML Noonan syndrome with multiple lentigines, ASD atrial septal defect, PVS pulmonary valve stenosis, NS Noonan syndrome, PDA patent duct arteriosus, DORV double outlet right ventricle, VSD ventricular septal defect, NA not available, LSVC left superior vena cava, CFCS cardiofaciocutaneous syndrome, CS Costello syndrome, NS/LAH Noonan syndrome with loose anagen hair
  2. aThe mutation identified in this study is in boldface