Key result
A novel indel mutation (c.1885_1889delinsGATCATCAACC) in the LDLR gene was identified in a Chinese family with familial hypercholesterolemia, which disrupted receptor trafficking and reduced LDL uptake to 30% of wild-type activity.
Why the study?
Does the novel indel variant c.1885_1889delinsGATCATCAACC in the LDLR gene cause familial hypercholesterolemia by disrupting receptor function?
Does the novel indel variant c.1885_1889delinsGATCATCAACC in the LDLR gene cause familial hypercholesterolemia by disrupting receptor function?
A novel indel mutation (c.1885_1889delinsGATCATCAACC) in the LDLR gene was identified as a pathogenic cause of familial hypercholesterolemia, expanding the spectrum of known LDLR mutations.
May support pathogenicity of this LDLR variant; extends mutation spectrum but leaves open need for clinical validation.
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.
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Shu et al. (2017) studied Familial hypercholesterolemia (n=114). LDLR c.1885_1889delinsGATCATCAACC mutation vs. Wild-type LDLR was evaluated on LDL uptake activity. A novel indel mutation (c.1885_1889delinsGATCATCAACC) in the LDLR gene was identified in a Chinese family with familial hypercholesterolemia, which disrupted receptor trafficking and reduced LDL uptake to 30% of wild-type activity.
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