Mutations in PCSK9 cause autosomal dominant hypercholesterolemia.
Autosomal dominant hypercholesterolemia (ADH; OMIM144400), a risk factor for coronary heart disease, is characterized by an increase in low-density lipoprotein cholesterol levels that is associated with mutations in the genes LDLR (encoding low-density lipoprotein receptor) or APOB (encoding apolipoprotein B). We mapped a third locus associated with ADH, HCHOLA3 at 1p32, and now report two mutations in the gene PCSK9 (encoding proprotein convertase subtilisin/kexin type 9) that cause ADH. PCSK9 encodes NARC-1 (neural apoptosis regulated convertase), a newly identified human subtilase that is highly expressed in the liver and contributes to cholesterol homeostasis.
INSERM U383, Hôpital Necker-Enfants Malades, AP-HP, Université Paris V, 149-161 rue de Sèvres, 75743 Paris Cedex 15, France.
Marianne
M
Abifadel
Mathilde
M
Varret
Jean-Pierre
JP
Rabès
Delphine
D
Allard
Khadija
K
Ouguerram
Martine
M
Devillers
Corinne
C
Cruaud
Suzanne
S
Benjannet
Louise
L
Wickham
Danièle
D
Erlich
Aurélie
A
Derré
Ludovic
L
Villéger
Michel
M
Farnier
Isabel
I
Beucler
Eric
E
Bruckert
Jean
J
Chambaz
Bernard
B
Chanu
Jean-Michel
JM
Lecerf
Gerald
G
Luc
Philippe
P
Moulin
Jean
J
Weissenbach
Annick
A
Prat
Michel
M
Krempf
Claudine
C
Junien
Nabil G
NG
Seidah
Catherine
C
Boileau
D019943:Amino Acid Substitution; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000201:enzymology / Q000235:genetics*; D008099:Liver / Q000201:enzymology; D008297:Male; D009154:Mutation; D010375:Pedigree; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases / Q000235:genetics*
C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases