|
P
|
G
|
Sb/Cs
|
Year of dg.
|
Age at death (†)/age at last follow up
|
First visceral symptoms (age)
|
First neuro-psychiatric symptoms (age)
|
BMS (Y/ND)
|
Filipin and CEL or CE (Y/ND)
|
Histology and AT (Y/ND)
|
Mutations (NPC1/NPC2†)predicted effect on protein
|
|---|
|
Age at dg.
|
|---|
|
Neonatal rapidly fatal form
|
|
1
|
M
|
B of 2/T2
|
1982
|
?(†)/1 m
|
NJa, Hp, HSm (1 m)
|
NR
|
Y
|
ND
|
Y
|
ND
|
|
<1y
|
|
2
|
M
|
B of 1/T2
|
1984
|
4 m (†)
|
NJa, Hp, HSm (1 m)
|
NR
|
Y
|
ND
|
Y (AT)
|
ND
|
|
<1y
|
|
3
|
M
|
0
|
1989
|
2 m (†)
|
NJa, Hp, HSm (1 m)
|
NR
|
ND
|
ND
|
Y (AT)
|
c.1261C>T/c.3614C>G††
|
|
<1y
|
p.Q421*/p.T1205R
|
|
Early infantile form
|
|
4
|
F
|
0
|
1976
|
5y (†)
|
HSm (1y)
|
PMRt (6 m)
|
ND
|
ND
|
Y (AT)
|
ND
|
|
5y
|
|
5
|
M
|
0
|
1981
|
5y (†)
|
NJa, HSm (1 m)
|
PMRt (1y)
|
Y
|
ND
|
Y (AT)
|
c.3557G>A/NDT
|
|
5y
|
p.R1186H/NDT
|
|
6
|
M
|
0
|
1983
|
4y (†)
|
NJa, Hp, HSm (1 m)
|
PMRg (1y)
|
Y
|
ND
|
Y (AT)
|
ND
|
|
1y
|
|
7
|
F
|
0
|
1985
|
11y (†)
|
mild HSm (1 m)
|
MRt (1y)
|
Y
|
Y (CE)
|
Y
|
c.3182T>C/c.3591+1G>A
|
|
1y
|
p.I1061T/splice
|
|
8
|
F
|
0
|
1990
|
4y (†)
|
HSm (20 m)
|
PMRg (20 m)
|
Y
|
Y (F/C)
|
ND
|
c.1812dupT/c.3558delC
|
|
3y
|
p.A605Cfs*1/p.A1187Rfs*54
|
|
9
|
F
|
0
|
1994
|
4y (†)
|
tachypnoea (1 m)
|
PMRt (1y)
|
Y
|
Y (F/C)
|
Y (AT)
|
NPC2: c.58G>T/c.58G>T
|
|
1y
|
p.E20*/p.E20*†
|
|
10
|
F
|
S of 10/T3
|
1997
|
?(†)/5y
|
NJa, HSm (1 m)
|
SRt (22 m)
|
Y
|
Y (F/C)
|
ND
|
c.826T>C/c.3557G>A
|
|
5y
|
p.Y276H/p.R1186H
|
|
11
|
F
|
0
|
2001
|
6y (†)
|
Sm (2y)
|
PMRg, A (22 m)
|
Y
|
Y (F/C)
|
Y (AT)
|
c.3557G>A/c.3614C>A
|
|
3y
|
p.R1186H/p.T1205K
|
|
12
|
F
|
S of 13/T3
|
2010
|
6y
|
HSm (2y)
|
PMRt, A (18 m)
|
ND
|
ND
|
ND
|
c.2196dupT
/c.3557G>A
p.P733Sfs*9
/p.R1186H
|
|
2y
|
- A ataxia, AT autopsy; B brother, BMS bone marrow smear; CE non-LDL-cholesterol esterification test; CEL LDL-cholesterol esterification test; Cs cousins, dg diagnosis, F female, F/C classical biochemical subtype using filipin staining + CEL, G gender, Hp hepatopathy, HSm hepatosplenomegaly, m months, M male, MRt motoric retardation, ND not done, NDT not detected, NR not reported, NJa neonatal jaundice, P order of patient in the age-at-onset category, PMRg psychomotoric regression, PMRt psychomotoric retardation, S sister, Sb sibling, Sm splenomegaly, SRt speech retardation, T table, y years, † patient deceased,†genotype refers to the NPC1 gene (patients 1–8 and 10–12), and to the NPC2 gene (patient 9),‡patient described previously[33],††genotype determined indirectly based on parents’ genotype. *translation stop codon in 1-letter amino acid code. Note: novel mutations are highlighted in bold font, and italics indicate decisive diagnostic method or methods (if they were performed simultaneously or in quick succession).
