A double heterozygote for familial hypercholesterolaemia and familial defective apolipoprotein B-100.

Abstract:

:Autosomal dominant hypercholesterolaemia is genetically heterogeneous, but most commonly (approximately 93%) caused by mutations in low-density lipoprotein receptor (LDLR), where the disease is known as familial hypercholesterolaemia (FH), or apolipoprotein B-100 (APOB) (approximately 5.5%), where the disease is known as familial defective APOB (FDB), while in approximately 2% of patients the mutation is in the proprotein convertase subtilisin/kexin type 9 gene. Homozygous FH having inheritance of two LDLR mutations is a rare but recognized syndrome associated with an extreme hypercholesterolaemia and early-onset coronary artery disease. We present a 15-year-old girl with untreated total cholesterol levels of 8.8 mmol/L who was heterozygous for both the LDLR p.Leu479Pro and APOB p.Arg3527Gln mutation. Cascade testing confirmed the paternal origin of the LDLR mutation and revealed a maternal diagnosis of FDB. This case provides further evidence that the combined effect of an LDLR and an APOB mutation give rise to a phenotype more severe than either mutation alone and is more severe than homozygous FDB, but less severe than homozygous FH. It also highlights the need to consider the presence of additional mutations in families where relatives have varying phenotypes.

journal_name

Ann Clin Biochem

authors

Taylor A,Bayly G,Patel K,Yarram L,Williams M,Hamilton-Shield J,Humphries SE,Norbury G

doi

10.1258/acb.2010.010089

subject

Has Abstract

pub_date

2010-09-01 00:00:00

pages

487-90

issue

Pt 5

eissn

0004-5632

issn

1758-1001

pii

acb.2010.010089

journal_volume

47

pub_type

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