TABLE 4.

Molecular and biochemical characterization of the NPC1 genetic mutations

Exon or Intron	Nucleotide Change	Mutation Type	Amino Acid Change	Protein Domainab	Biochemical Phenotypec	Sample Numberd
2	72delC	Frameshift				1
3	221G>A	Missense	C74Y	LM A	Severe	2
3	275A>G	Missense	Q92R	LM A	Severe	1
4	410C>T	Missense	T137M	LM A	Variable	3
4	395delC	Frameshift				1
4	451_452delAG	Frameshift				2
5	496C>T	Missense	P166S	LM A		1
6	688_693del6bp	Deletion/Insertion	S230_V231del	LM A	Classical	3
6	740G>A	Missense	C247Y	LM A	Severe	1
8	1201C>A	Missense	P401T	LM C		1
8	974_975insGA	Frameshift				1
8	1211G>A	Missense/Splicing	R404Q	LM C	Severe	3
8	1261C>T	Nonsense	Q421X			1
8	1298C>T	Missense	P433L	LM C		1
9	1421C>T	Missense	P474L	LM C	Classical/Variant	1
9	1526A>C	Missense	Y509S	LM C		1
10	1628C>T	Missense	P543L	LM C		2
12	1836A>C	Missense	E612D	LM C	Severe	1
12		Missense	Y628C	TM III, SSD		1 (N)
13	1955C>G	Missense	S652W	CP D, SSD	Severe	3
13	1978G>A	Missense	G660S	TM IV, SSD	Moderate	1
13		Missense	G673V	TM IV, SSD		1
13	2098G>A	Missense	D700N	TM V, SSD	Severe	2
15	2336_2337insT	Frameshift				2
15	2365C>T	Missense	R789G	CP H, SSD	Severe	1
16	2474A>G	Missense	Y825C	CP H	Severe	2
18	2621A>T	Missense	D874V	LM I	Classical/Severe	2
18		Missense	P887L	LM I		1 (N)
18	2669G>A	Missense	Y890C	LM I	Classical	2
19		Missense	I923V	LM I		1 (N)
19	2819C>T	Missense	S940L	LM I	Variable	3
19	2833G>A	Missense	D945N	LM I	Severe	2
19	2848G>A	Missense	V950M	LM I	Variant	2
20	2926T>C	Splicing	C976R			2
IVS20	IVS20(-2)insG	Splicing				1
20	3019C>G	Missense	P1007A	LM I	Moderate/Variant	3
IVS21	IVS21(-10)delTCC	Splicing				1
21	3107C>T	Missense	T1036M	LM I	Severe	4
21	3182T>C	Missense	I1061T	LM I	Classical/Variable	21
22	3259T>C	Missense	F1087L	LM I		1
22	3265G>A	Missense	E1089K	LM I		2
22		Missense	A1151T	TM XI		1 (N)
22	3467A>G	Missense	N1156S	TM XI	Moderate	2
23	3493G>A	Missense	V1165M	CP L		1
23	3566A>G	Missense	E1189G	CP L	Severe	1
23	3573_3574insACTT	Frameshift				1
24	3612_3613insGdelTA	Frameshift				1
24	3662delT	Frameshift				2
24	3741_3744delACTC	Frameshift				1 (N)
24	3742_3745delCTCA	Frameshift				1
24	3745A>G	Missense	S1249G	TM XIII	Severe	1
25	3797G>A	Missense	R1266Q	CP N		1 (P)

Novel mutations are indicated in bold-face type.

^aProtein domains are provided for missense and deletion/insertion amino acid changes where known, as previously indicated (30).

^bThe lumen (LM), transmembrane (TM), cytoplasmic (CP), and sterol sensing (SSD) protein domains are provided as previously indicated (30, 53).

^cThe biochemical phenotypes of respective nucleotide and/or amino acid changes are based upon the degree of cholesterol esterification catalyzed by acyl-CoA:cholesterol acyltransferase (ACAT), and were provided for known nucleotide and/or amino acid changes as previously indicated (30).

^dNumber of respective variations within the sample of NPC1 patients are provided, whereby polymorphisms (P) and novel (N) mutations are indicated.