Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein

Christine Kim Garcia, Kenneth Wilund, Marcello Arca, Giovanni Zuliani, Renato Fellin, Mario Maioli, Sebastiano Calandra, Stefano Bertolini, Fausto Cossu, Nick Grishin, Robert Barnes, Jonathan C. Cohen, Helen H. Hobbs

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1394-1398
Number of pages5
JournalScience
Volume292
Issue number5520
DOIs
StatePublished - May 18 2001

ASJC Scopus subject areas

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    Garcia, C. K., Wilund, K., Arca, M., Zuliani, G., Fellin, R., Maioli, M., Calandra, S., Bertolini, S., Cossu, F., Grishin, N., Barnes, R., Cohen, J. C., & Hobbs, H. H. (2001). Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein. Science, 292(5520), 1394-1398. https://doi.org/10.1126/science.1060458