TY - JOUR
T1 - Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein
AU - Garcia, Christine Kim
AU - Wilund, Kenneth
AU - Arca, Marcello
AU - Zuliani, Giovanni
AU - Fellin, Renato
AU - Maioli, Mario
AU - Calandra, Sebastiano
AU - Bertolini, Stefano
AU - Cossu, Fausto
AU - Grishin, Nick
AU - Barnes, Robert
AU - Cohen, Jonathan C.
AU - Hobbs, Helen H.
PY - 2001/5/18
Y1 - 2001/5/18
N2 - Atherogenic low density lipoproteins are cleared from the circulation by hepatic low density lipoprotein receptors (LDLR). Two inherited forms of hypercholesterolemia result from loss of LDLR activity: autosomal dominant familial hypercholesterolemia (FH), caused by mutations in the LDLR gene, and autosomal recessive hypercholesterolemia (ARH), of unknown etiology. Here we map the ARH locus to a ∼1-centimorgan interval on chromosome 1p35 and identify six mutations in a gene encoding a putative adaptor protein (ARH). ARH contains a phosphotyrosine binding (PTB) domain, which in other proteins binds NPXY motifs in the cytoplasmic tails of cell-surface receptors, including the LDLR. ARH appears to have a tissue-specific role in LDLR function, as it is required in liver but not in fibroblasts.
AB - Atherogenic low density lipoproteins are cleared from the circulation by hepatic low density lipoprotein receptors (LDLR). Two inherited forms of hypercholesterolemia result from loss of LDLR activity: autosomal dominant familial hypercholesterolemia (FH), caused by mutations in the LDLR gene, and autosomal recessive hypercholesterolemia (ARH), of unknown etiology. Here we map the ARH locus to a ∼1-centimorgan interval on chromosome 1p35 and identify six mutations in a gene encoding a putative adaptor protein (ARH). ARH contains a phosphotyrosine binding (PTB) domain, which in other proteins binds NPXY motifs in the cytoplasmic tails of cell-surface receptors, including the LDLR. ARH appears to have a tissue-specific role in LDLR function, as it is required in liver but not in fibroblasts.
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U2 - 10.1126/science.1060458
DO - 10.1126/science.1060458
M3 - Article
C2 - 11326085
AN - SCOPUS:0035906961
SN - 0036-8075
VL - 292
SP - 1394
EP - 1398
JO - Science
JF - Science
IS - 5520
ER -