Open AccessA novel indel variant in LDLR responsible for familial hypercholesterolemia in a Chinese family
Author(s) -
Hongyan Shu,
Jen-Tsan Chi,
Jing Li,
Wei Zhang,
Wenshan Lv,
Jie Wang,
Yujie Deng,
Xu Hou,
Yangang Wang
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0189316
Subject(s) - familial hypercholesterolemia , ldl receptor , indel , mutant , mutation , genetics , biology , phenotype , gene , cholesterol , lipoprotein , endocrinology , genotype , single nucleotide polymorphism
Familial hypercholesterolemia (FH) is an inherited disorder characterized by elevation of serum cholesterol bound to low-density lipoprotein. Mutations in LDLR are the major factors responsible for FH. In this study, we recruited a four-generation Chinese family with FH and identified the clinical features of hypercholesterolemia. All affected individuals shared a novel indel mutation (c.1885_1889delinsGATCATCAACC) in exon 13 of LDLR . The mutation segregated with the hypercholesterolemia phenotype in the family. To analyze the function of the indel, we established stable clones of mutant and wild-type LDLR in Hep G2 cells. The mutant LDLR was retained in the endoplasmic reticulum (ER) and failed to glycosylate via the Golgi. Moreover, the membrane LDLR was reduced and lost the ability to take up LDL. Our data also expand the spectrum of known LDLR mutations.