title: 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.
authors: Division of Endcrinology and Metabolism, Diabetes Center, Department of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors: Xiao Li
authors: XL
authors: Wang
authors: Jun-ichi
authors: J
authors: Osuga
authors: Fumiko
authors: F
authors: Tazoe
authors: Kenta
authors: K
authors: Okada
authors: Shuichi
authors: S
authors: Nagashima
authors: Manabu
authors: M
authors: Takahashi
authors: Taichi
authors: T
authors: Ohshiro
authors: Tumenbayar
authors: T
authors: Bayasgalan
authors: Hiroaki
authors: H
authors: Yagyu
authors: Koji
authors: K
authors: Okada
authors: Shun
authors: S
authors: Ishibashi