HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ameis, D. Articles by Greten, H. Search for Related Content PubMed PubMed Citation Articles by Ameis, D. Articles by Greten, H. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol 36, 241-250, Copyright © 1995 by Lipid Research, Inc.

ARTICLES

A 5' splice-region mutation and a dinucleotide deletion in the lysosomal acid lipase gene in two patients with cholesteryl ester storage disease

D Ameis, G Brockmann, R Knoblich, M Merkel, RE Ostlund Jr, JW Yang, PM Coates, JA Cortner, SV Feinman and H Greten
Department of Medicine, University Hospital Eppendorf, Hamburg, Germany.

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.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Muntoni, H. Wiebusch, M. Jansen-Rust, S. Rust, U. Seedorf, H. Schulte, K. Berger, H. Funke, and G. Assmann Prevalence of Cholesteryl Ester Storage Disease Arterioscler. Thromb. Vasc. Biol., August 1, 2007; 27(8): 1866 - 1868. [Full Text] [PDF]

				O. Zschenker, C. Bahr, U.-F. Hess, and D. Ameis Systematic Mutagenesis of Potential Glycosylation Sites of Lysosomal Acid Lipase J. Biochem., March 1, 2005; 137(3): 387 - 394. [Abstract] [Full Text] [PDF]

				O. Zschenker, N. Jung, J. Rethmeier, S. Trautwein, S. Hertel, M. Zeigler, and D. Ameis Characterization of lysosomal acid lipase mutations in the signal peptide and mature polypeptide region causing Wolman disease J. Lipid Res., July 1, 2001; 42(7): 1033 - 1040. [Abstract] [Full Text] [PDF]

				P. Lohse, S. Maas, P. Lohse, M. Elleder, J. M. Kirk, G. T. N. Besley, and D. Seidel Compound heterozygosity for a Wolman mutation is frequent among patients with cholesteryl ester storage disease J. Lipid Res., January 1, 2000; 41(1): 23 - 31. [Abstract] [Full Text]

				A. Roussel, S. Canaan, M.-P. Egloff, M. Riviere, L. Dupuis, R. Verger, and C. Cambillau Crystal Structure of Human Gastric Lipase and Model of Lysosomal Acid Lipase, Two Lipolytic Enzymes of Medical Interest J. Biol. Chem., June 11, 1999; 274(24): 16995 - 17002. [Abstract] [Full Text] [PDF]

				P. Lohse, S. Maas, P. Lohse, A. C. Sewell, O. P. van Diggelen, and D. Seidel Molecular defects underlying Wolman disease appear to be more heterogeneous than those resulting in cholesteryl ester storage disease J. Lipid Res., February 1, 1999; 40(2): 221 - 228. [Abstract] [Full Text]

				F. Pagani, R. Pariyarath, R. Garcia, C. Stuani, A. B. Burlina, G. Ruotolo, M. Rabusin, and F. E. Baralle New lysosomal acid lipase gene mutants explain the phenotype of Wolman disease and cholesteryl ester storage disease J. Lipid Res., July 1, 1998; 39(7): 1382 - 1388. [Abstract] [Full Text]

				S. Sheriff, H. Du, and G. A. Grabowski Characterization of Lysosomal Acid Lipase by Site-directed Mutagenesis and Heterologous Expression J. Biol. Chem., November 17, 1995; 270(46): 27766 - 27772. [Abstract] [Full Text] [PDF]