Familial Hypobetalipoproteinemia Caused by Homozygous Loss-of-function Mutations in PCSK9: A Case Report

Elsevier

Available online 25 July 2022

Journal of Clinical LipidologyHighlights•

We present a case with FHBL caused by homozygous LOF mutations in PCSK9.

A novel missense mutation in PCSK9 was associated with reduced serum PCSK9 level.

She had no complications, except for mild fatty liver.

Abstract

Here, we present the first case of a Japanese patient with familial hypobetalipoproteinemia (HBL) that is caused by homozygous loss-of-function mutations in proprotein convertase subtilisin/kexin type 9 (PCSK9). A 46-year-old female patient who was born in a consanguineous marriage of parents who were second cousins was referred to our hospital due to decreased low-density lipoprotein (LDL)-cholesterolemia (22 mg/dL). She did not have any secondary HBL causes. Novel homozygous mutations were identified in PCSK9 (c.1133G>A [p.Cys378Tyr]) using panel sequencing. The serum levels of heterodimer PCSK9 and furin-cleaved PCSK9 were extremely low (<32 and 15 ng/mL, respectively), leading to the diagnosis of familial HBL diagnosis caused by loss-of-function mutations in PCSK9. The patient did not exhibit any complications associated with low LDL cholesterol, except for mild fatty liver and reduced serum 25-OH vitamin D level (15.7 ng/mL). Here, we provide a detailed molecular and functional characterization of a novel loss-of-function mutation in PCSK9.

Keywords

hypobetalipoproteinemia (HBL)

FHBL

PCSK9

LDL cholesterol

genetics

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© 2022 Published by Elsevier Inc. on behalf of National Lipid Association.

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