Table 2 Comparison of two patient’s findings to 16 other cases of CHD8 heterozygous missense /nonsense mutations that have been reported in the Human Gene Mutation Database

Features

Patient 1

Patient 2

1[8]

2[19]

3[19]

4[25]

5[17]

6[17]

7[17]

Sex

M

M

M

M

M

M

M

M

M

Age (months)

24

28

96

48

60

216

72

N/A

84

Mutation

Nonsense

Missense

Nonsense

Nonsense

Nonsense

Nonsense

Nonsense

Missense

Missense

Nucleotide/Protein

c.2647C > A/p.E883X

c.1677C > A/p.M559I

c.3712C > T/p.Q1238

c.185C > G/p.S62

c.4009C > T/p.R1337

c.6518C > A/p.S2173

c.2729G > A/p.R910Q

c.3340G > T/p.E1114

c.5129G > T/p.G1710 V

Inheritance

dn

dn

dn

dn

N/A

N/A

dn

N/A

Inherited Maternal

Developmental delay

+

+

+

+

+

–

+

N/A

+

Intellectual disability

+

+

+

–

–

–

+

N/A

N/A

Verbal IQ

N/A

N/A

20

75

79

N/A

27

N/A

N/A

Non-verbal IQ

N/A

N/A

34

78

92

N/A

41

N/A

N/A

Autism

+

+

+

+

+

Schizophrenia

+

Intellectual disability

+

Macrocephaly

+

–

+

–

+

N/A

+

N/A

–

Gastrointestinal

+

+

+

+

+

–

+

N/A

–

Constipation Abdominal pain

Chronic constipationand loose stool

Constipatio Diarrhea

Constipatio Diarrhea

Features

8[17]

9[26]

10[27]

11[28]

12[29]

13[29]

14[29]

15[29]

16[29]

Sex

M

M

M

M

Age (months)

204

36

264

96

Mutation

Missense

Nonsense

Missense

Missense

Missense

Missense

Missense

Missense

Nonsense

Nucleotide/Protein

c.5390G > A/p.R1797Q

c.5500C > T/p.R1834

c.2230G > A/p.V744I

c.3979G > A/p.E1327K

c.856C > T/p.R286C

c.6472C > T/p.R2158C

c.6538C > T/p.R2180C

c.6830G > C/p.G2277A

c.6941G > A/p.R2314Q

Inheritance

Inherited Patenal

dn

dn

dn

N/A

N/A

N/A

N/A

N/A

Developmental delay

N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

Intellectual disability

_

+

+

+

N/A

N/A

N/A

N/A

N/A

Verbal IQ

76

N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

Non-verbal IQ

95

N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

Autism

+

+

+

–

+

+

+

+

+

Macrocephaly

–

N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

Gastrointestinal

+

N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

Diarrhea Constipation