Table 1 Clinical and molecular findings in 12 Chinese NP-C patients

1

early infantile

F

frequent falls, 1y

delayed motor/neuron development, splenomegaly

1 y

4 y

NPC1

c.1501G>T + c.1800delC

E9 + E12

p.D501Y + p.I601FfsX13

16

97

foam cells

391.6

2

F

splenomegaly, 6 m

splenomegaly, global developmental delay, diarrhea, seizure at 7 y, cerebral atrophy on brain imaging

1 y

8 y

NPC2

c.3G>C + IVS2 + 5G > A

E1 + IVS2

p.M1I + IVS2 + 5G > A

4

66

foam cells

220.8

3

M

splenomegaly, 1y

splenomegaly, frequent falls when started independent walking at 1.5 y, congenital cleft lip and palate, language delay, gelastic cataplexy from 2.5 y, positive family history

1.5 y

3 y

NPC1

c.416_417insC + c.1832A>G

E3 + E12

p.N140KfsX30 + p.D611G

10

72

foam cells

602.7

4

M

prolonged jaundice,15 ds after birth

prolonged jaundice, hepatosplenomegaly, frequent falls when started independent walking at 1 y, slower intelligence progression, psychomotor regression and gelastic cataplexy from 3 y

1 y

5 y 10 m

NPC1

c.2177G>C + c.3734_3735delCT

E14 + E24

p.R726T + p.P1245RfsX12

149*

301*

foam cells

445.8

5

M

delayed independent walk, 1y8m

slow motor development, hepatosplemegaly, psychomotor regression at 2 y

1 y 8 m

2 y 2 m

NPC1

c.2230_2231delGT + c.3734_3735delCT

E14 + E24

p.V744SfsX27 + p.P1245RfsX12

27

83

foam cells

417.5

6

F

frequent falls,1y3m

frequent falls when walking, gelastic cataplexy, motor regression at 3 y, splenomegaly

1 y 3 m

7y

NPC1

c.1553G>A + c.2795dupA

E9 + E18

p.R518Q + p.Y932X

15

75

foam cells

161.7

7

M

frequent falls, 1y8m

frequent falls when walking, gelastic cataplexy, splenomegaly, younger brother of patient 6

1 y 8 m

3y7m

NPC1

c.1553G>A + c.2795dupA

E9 + E18

p.R518Q + p.Y932X

N.D

N.D

N.D

101.6

8

late infantile

M

hepatosplenomegaly, 1y8m

hepatosplemegaly, thrombocytopenia, psychomotor regression at 2.5 y

2 y 6 m

1 y 8 m

NPC1

c.2302_2303insG + c.2912-3C>G

E15 + IVS19

p.V768GfsX4 + c.2912-3C > G

24

75

foam cells

150.6

9

juvenile

M

ataxia, 8ys

ataxia, progressively loss of memory, loss of language at 9 ys, seizure from 12 y, thrombocytopenia without splenomegaly

8 y

13 y

NPC1

c. 1502A>T + c. 3634G>T

E9 + E24

p.D501V + p.V1212L

10

59

N.D

108

10

adult

M

visual and auditory hallucination, 16 ys

schizophrenia-like psychosis, splenomegaly deteced by abdominal ultrasound, intestinal constipation

16 y

20 y

NPC1

c.2366G>A + c.2972_2973delAG

E15 + E20

p.R789H + p.Q991RfsX15

34.7

39.6

N.D

32

11

unknown

M

delayed jaundice regression, 1 m

delayed jaundice regression, increasing splenomegaly, mild hepatomegaly

N.A

14 m

NPC1

c.2054T>C + c.2128C>T

E13 + E13

p.I685T + p.Q710X

59*

145*

foam cells

456.3

12

F

splenomegaly, 3y3m

isolated splenomegaly

N.A

3y5m

NPC1

c.1030del>T + c.2861C>T

E8 + E19

p.S344KfsX105 + p.S954L

N.D

N.D

N.D

232.3