A novel frameshift mutation of the lecithin:cholesterol acyltransferase (LCAT) gene associated with renal failure in familial LCAT deficiency.

Background: The lecithin:cholesterol acyltransferase (LCAT) gene is located on the long arm of chromosome 16 and encodes a highly conserved enzyme that catalyzes the formation of most plasma lipoprotein cholesteryl esters. Two autosomal recessive disorders, familial LCAT deficiency (FLD) and fish eye disease, are associated with germline LCAT mutations. Patients with FLD and fish-eye disease frequently present with corneal opacity, anemia and renal failure with proteinuria.

Methods: We clinically and biochemically characterized a German patient with classical FLD and used molecular genetic analysis to identify a novel homozygous LCAT mutation within codon 178.

Results: The insertion of adenine identified is located in one of the two motifs that resemble sequences found in several lipases, and results in a frameshift with a stop codon at residue 214. Therefore, the mutation alters a large portion of the LCAT enzyme, including both protein regions with putative lipase activity. Clinically, the female patient presented with corneal opacity, mild anemia and a slow deterioration in kidney function that led to a requirement for hemodialysis until she received a renal transplant.

Conclusions: The present data provide additional insights into the genotype/phenotype correlations of FLD and thus may improve the genetic diagnosis of this interesting inborn error of metabolism.