TY - JOUR
T1 - Mutations in STAP1 are associated with autosomal dominant hypercholesterolemia
AU - Fouchier, Sigrid W.
AU - Dallinga-Thie, Geesje M.
AU - Meijers, Joost C. M.
AU - Zelcer, Noam
AU - Kastelein, John J. P.
AU - Defesche, Joep C.
AU - Hovingh, G. Kees
PY - 2014
Y1 - 2014
N2 - Autosomal-dominant hypercholesterolemia (ADH) is characterized by elevated low-density lipoprotein cholesterol levels and increased risk for coronary vascular disease. ADH is caused by mutations in the low-density lipoprotein receptor, apolipoprotein B, or proprotein convertase subtilisin/kexin 9. A number of patients, however, suffer from familial hypercholesterolemia 4 (FH4), defined as ADH in absence of mutations in these genes and thereafter use the abbreviation FH4. To identify a fourth locus associated with ADH. Parametric linkage analysis combined with exome sequencing in a FH4 family resulted in the identification of the variant p.Glu97Asp in signal transducing adaptor family member 1 (STAP1), encoding signal transducing adaptor family member 1. Sanger sequencing of STAP1 in 400 additional unrelated FH4 probands identified a second p.Glu97Asp carrier and 3 additional missense variants, p.Leu69Ser, p.Ile71Thr, and p.Asp207Asn. STAP1 carriers (n=40) showed significantly higher plasma total cholesterol and low-density lipoprotein cholesterol levels compared with nonaffected relatives (n=91). We mapped a novel ADH locus at 4p13 and identified 4 variants in STAP1 that associate with ADH
AB - Autosomal-dominant hypercholesterolemia (ADH) is characterized by elevated low-density lipoprotein cholesterol levels and increased risk for coronary vascular disease. ADH is caused by mutations in the low-density lipoprotein receptor, apolipoprotein B, or proprotein convertase subtilisin/kexin 9. A number of patients, however, suffer from familial hypercholesterolemia 4 (FH4), defined as ADH in absence of mutations in these genes and thereafter use the abbreviation FH4. To identify a fourth locus associated with ADH. Parametric linkage analysis combined with exome sequencing in a FH4 family resulted in the identification of the variant p.Glu97Asp in signal transducing adaptor family member 1 (STAP1), encoding signal transducing adaptor family member 1. Sanger sequencing of STAP1 in 400 additional unrelated FH4 probands identified a second p.Glu97Asp carrier and 3 additional missense variants, p.Leu69Ser, p.Ile71Thr, and p.Asp207Asn. STAP1 carriers (n=40) showed significantly higher plasma total cholesterol and low-density lipoprotein cholesterol levels compared with nonaffected relatives (n=91). We mapped a novel ADH locus at 4p13 and identified 4 variants in STAP1 that associate with ADH
U2 - https://doi.org/10.1161/CIRCRESAHA.115.304660
DO - https://doi.org/10.1161/CIRCRESAHA.115.304660
M3 - Article
C2 - 25035151
SN - 0009-7330
VL - 115
SP - 552
EP - 555
JO - Circulation Research
JF - Circulation Research
IS - 6
ER -