A NOVEL MISSENSE MUTATION (ASN(5)-]ILE) IN LECITHIN-CHOLESTEROL ACYLTRANSFERASE (LCAT) GENE IN A JAPANESE PATIENT WITH LCAT DEFICIENCY

We identified a novel missense mutation in the lecithin:cholesterol ac yltransferase gene in a new case of lecithin: cholesterol acyltransfer ase (LCAT) deficiency. The patient was a 64-year-old diabetic Japanese male who showed an extremely low level of serum high-density lipoprot ein-cholesterol, corneal opacities, anemia, and proteinuria. Both the patient's LCAT activity and mass were markedly low. DNA sequence analy sis of the LCAT gene showed an A-to-T transition at base 97 in exon 1, and predicted a change in asparagine to isoleucine at the 5th amino a cid of the protein. Restriction analysis of polymerase chain reaction- amplified DNA using Ase I showed that the patient was homozygous for t his mutation. Our results suggested that asparagine 5 was an important amino acid and substitution with isoleucine caused marked reduction o f LCAT activity and mass, resulting in LCAT deficiency.