Molecular analysis of a novel LCAT mutation (Gly179 → Arg) found in a patient with complete LCAT deficiency.

Abstract:

:Lecithin-cholesterol acyltransferase (LCAT) is an important enzyme involved in the esterification of cholesterol. Here, we report a novel point mutation in the LCAT gene of a 63-year-old female with characteristics of classic familial LCAT deficiency. The patient's clinical manifestations included corneal opacity, mild anemia, mild proteinuria and normal renal function. She had no sign of coronary heart disease. Her LCAT activity was extremely low. DNA sequencing revealed a point mutation in exon 5 of the LCAT gene: a G to C substitution converting Gly(179) to an Arg, located in one of the catalytic triads of the enzyme. In vitro expression of recombinant LCAT proteins in HEK293 cells showed that the mutant G179R protein was present in the cell lysate, but not the culture medium. LCAT activity was barely detectable in the cell lysate or medium of the cells expressing the G179R mutant. This novel missense mutation seems to cause a complete loss of catalytic activity of LCAT, which is also defective in secretion.

journal_name

J Atheroscler Thromb

authors

Wang XL,Osuga J,Tazoe F,Okada K,Nagashima S,Takahashi M,Ohshiro T,Bayasgalan T,Yagyu H,Okada K,Ishibashi S

doi

10.5551/jat.8003

subject

Has Abstract

pub_date

2011-01-01 00:00:00

pages

713-9

issue

8

eissn

1340-3478

issn

1880-3873

pii

JST.JSTAGE/jat/8003

journal_volume

18

pub_type

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