Ameis_1995_J.Lipid.Res_36_241

Reference

Title : A 5' splice-region mutation and a dinucleotide deletion in the lysosomal acid lipase gene in two patients with cholesteryl ester storage disease - Ameis_1995_J.Lipid.Res_36_241
Author(s) : Ameis D , Brockmann G , Knoblich R , Merkel M , Ostlund RE, Jr. , Yang JW , Coates PM , Cortner JA , Feinman SV , Greten H
Ref : J Lipid Res , 36 :241 , 1995
Abstract :

Cholesteryl ester storage disease (CESD) results from inherited deficiencies of the lysosomal hydrolase, acid lipase (LAL; E.C. 3.1.1.13). To establish the molecular defects in LAL deficiency, two unrelated probands with severely reduced LAL activity were examined. DNA amplification by reverse-transcription polymerase chain reaction and subsequent sequence analysis of LAL cDNA identified two mutant alleles. Patient 1, presenting with hepatosplenomegaly, mildly elevated liver function tests, and hyperlipidemia, was homozygous for a deletion of nucleotides 823 to 894 of the LAL cDNA. This 72-bp deletion maintained the reading frame and resulted in a loss of 24 amino acids from the LAL protein. Analysis of genomic DNA revealed that the 72 bp corresponded to an exon of the LAL gene. A single G to A point mutation at the last exon position was observed in the genomic DNA of patient 1, indicating a splicing defect with consecutive exon skipping underlying the 72-bp deletion. Patient 2 was a compound heterozygote for the 72-bp deletion and a dinucleotide deletion at positions 967 and 968. This deletion resulted in a shifted reading frame carboxyterminal of codon 296, and 43 random amino acids followed the frame shift. A premature stop at codon 339 truncated the mutant LAL protein by 34 amino acids. Allele-specific hybridization confirmed that patient 1 was homozygous for the 72-bp deletion mutation, and that patient 2 was a compound heterozygote for the 72-bp deletion and the 2-bp deletion.

PubMedSearch : Ameis_1995_J.Lipid.Res_36_241
PubMedID: 7751811
Gene_locus related to this paper: human-LIPA

Related information

Mutation S275_Q298del_human-LIPA
Gene_locus human-LIPA

Citations formats

Ameis D, Brockmann G, Knoblich R, Merkel M, Ostlund RE, Jr., Yang JW, Coates PM, Cortner JA, Feinman SV, Greten H (1995)
A 5' splice-region mutation and a dinucleotide deletion in the lysosomal acid lipase gene in two patients with cholesteryl ester storage disease
J Lipid Res 36 :241

Ameis D, Brockmann G, Knoblich R, Merkel M, Ostlund RE, Jr., Yang JW, Coates PM, Cortner JA, Feinman SV, Greten H (1995)
J Lipid Res 36 :241