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High-Throughput Microscopy Characterization of Rare LDLR Variants.

ABSTRACT: Familial hypercholesterolemia (FH) is the most common inherited life-threatening disorder of lipid metabolism. Early diagnosis and treatment are the key to reduce the cumulative life-long cardiovascular burden of patients with FH. The high number of LDLR variants described as variants of unknown significance is the largest obstacle to achieve a definitive FH diagnosis. This study established a time- and cost-effective high-throughput cell-based assay to functionally profile LDLR variants, which allowed us to discriminate disruptive rare variants from silent ones. This work generated a valuable resource for systematic functional characterization of LDLR variants solving 1 of the major issues to achieve a definitive FH diagnosis.

SUBMITTER: Graca R

PROVIDER: S-EPMC10504398 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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High-Throughput Microscopy Characterization of Rare LDLR Variants.

Graça Rafael R Zimon Magdalena M Alves Ana C AC Pepperkok Rainer R Bourbon Mafalda M

JACC. Basic to translational science 20230628 8

Familial hypercholesterolemia (FH) is the most common inherited life-threatening disorder of lipid metabolism. Early diagnosis and treatment are the key to reduce the cumulative life-long cardiovascular burden of patients with FH. The high number of LDLR variants described as variants of unknown significance is the largest obstacle to achieve a definitive FH diagnosis. This study established a time- and cost-effective high-throughput cell-based assay to functionally profile LDLR va ...[more]

PMID: 37719435

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