Available online 25 July 2022
Highlights•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.
AbstractHere, 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.
Keywordshypobetalipoproteinemia (HBL)
FHBL
PCSK9
LDL cholesterol
genetics
View full text© 2022 Published by Elsevier Inc. on behalf of National Lipid Association.
留言 (0)