A novel lysosomal acid lipase gene mutation in a patient with cholesteryl ester storage disease.

The molecular defects in the gene encoding the lysosomal acid lipase (LAL) were investigated in an adult male patient affected with cholesteryl ester storage disease (CESD), an autosomal recessive disorder associated with LAL deficient activity. Nucleotide sequencing of amplified LAL genomic DNA or reverse-transcribed mRNA demonstrated that this patient was a compound heterozygote for a previously reported mutation, a G-->A transition at position -1 of the exon 8 splice donor site, resulting in skipping of the complete exon 8, and for a C-->T substitution at position 233 (exon 3), which introduces a premature in-frame termination codon. This yet undescribed mutation, which results in the loss of 89% of LAL amino acids, is very likely to abolish the LAL catalytic activity.