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.
Abifadel
Marianne
M
INSERM U383, Hôpital Necker-Enfants Malades, AP-HP, Université Paris V, 149-161 rue de Sèvres, 75743 Paris Cedex 15, France.
Varret
Mathilde
M
Rabès
Jean-Pierre
JP
Allard
Delphine
D
Ouguerram
Khadija
K
Devillers
Martine
M
Cruaud
Corinne
C
Benjannet
Suzanne
S
Wickham
Louise
L
Erlich
Danièle
D
Derré
Aurélie
A
Villéger
Ludovic
L
Farnier
Michel
M
Beucler
Isabel
I
Bruckert
Eric
E
Chambaz
Jean
J
Chanu
Bernard
B
Lecerf
Jean-Michel
JM
Luc
Gerald
G
Moulin
Philippe
P
Weissenbach
Jean
J
Prat
Annick
A
Krempf
Michel
M
Junien
Claudine
C
Seidah
Nabil G
NG
Boileau
Catherine
C
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