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 Biochemjournal_title
Annals of clinical biochemistryauthors
Taylor A,Bayly G,Patel K,Yarram L,Williams M,Hamilton-Shield J,Humphries SE,Norbury Gdoi
10.1258/acb.2010.010089subject
Has Abstractpub_date
2010-09-01 00:00:00pages
487-90issue
Pt 5eissn
0004-5632issn
1758-1001pii
acb.2010.010089journal_volume
47pub_type
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journal_title:Annals of clinical biochemistry
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