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 Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Huang, L. S. Articles by Breslow, J. L. Search for Related Content PubMed PubMed Citation Articles by Huang, L. S. Articles by Breslow, J. L. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol 32, 1341-1348, Copyright © 1991 by Lipid Research, Inc.

ARTICLES

ApoB gene nonsense and splicing mutations in a compound heterozygote for familial hypobetalipoproteinemia

LS Huang, H Kayden, RJ Sokol and JL Breslow
Laboratory of Biochemical Genetics and Metabolism, Rockefeller University, New York, NY 10021.

Two novel apoB gene mutations were identified in a patient (CM) with phenotypic homozygous hypobetalipoproteinemia. Haplotype analysis of the apoB alleles from this patient and his family members revealed him to be a genetic compound for the disease. In contrast to previous studies of other hypobetalipoproteinemic patients, no clues existed as to where in the apoB gene the molecular defects resided. Therefore, it was necessary to characterize the apoB genes of the patient by sequence analysis. The apoB gene contains 29 exons and is 43 kb in length. The gene encodes a 14.1 kb mRNA and a 4563 amino acid protein. Both apoB alleles from the patient were cloned via 26 sets of polymerase chain reactions (PCR). These clones contained a total of approximately 24 kb of apoB gene sequence, including regions 5' and 3' to the coding region, 29 exons, and the intron/exon junctions. Complete DNA sequence analysis of these clones showed that each apoB allele had a mutation. In the paternal apoB allele, there was a splicing mutation. The first base of the dinucleotide consensus sequence (GT) in the 5' splice donor site in intron 5 was replaced by a T. It is likely that this base substitution interferes with proper splicing and results in the observed absence of plasma apoB. In the maternal apoB allele, there was a nonsense mutation. The first base of the Arg codon (CGA) at residue 412 in exon 10 was replaced by a T, resulting in a termination codon (TGA). The nonsense mutation is likely to terminate translation after residue 411 resulting in a severely truncated protein only 9% of the length of B-100.(ABSTRACT TRUNCATED AT 250 WORDS)
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				E. Di Leo, L. Magnolo, S. Lancellotti, L. Croce, L. Visintin, C. Tiribelli, S. Bertolini, S. Calandra, and P. Tarugi Abnormal apolipoprotein B pre-mRNA splicing in patients with familial hypobetalipoproteinaemia J. Med. Genet., March 1, 2007; 44(3): 219 - 224. [Abstract] [Full Text] [PDF]

				Z. Chen, R. L Fitzgerald, and G. Schonfeld Hypobetalipoproteinemic Mice with a Targeted Apolipoprotein (Apo) B-27.6-specifying Mutation. IN VIVO EVIDENCE FOR AN IMPORTANT ROLE OF AMINO ACIDS 1254-1744 OF ApoB IN LIPID TRANSPORT AND METABOLISM OF THE ApoB-CONTAINING LIPOPROTEIN J. Biol. Chem., April 12, 2002; 277(16): 14135 - 14145. [Abstract] [Full Text] [PDF]

				F. K. Welty, K. A. Guida, and J. J. Andersen Donor Splice-Site Mutation (210+1G_C) in the ApoB Gene Causes a Very Low Level of ApoB-100 and LDL Cholesterol Arterioscler. Thromb. Vasc. Biol., November 1, 2001; 21(11): 1864 - 1865. [Full Text] [PDF]

				P. Tarugi, A. Lonardo, C. Gabelli, F. Sala, G. Ballarini, I. Cortella, L. Previato, S. Bertolini, R. Cordera, and S. Calandra Phenotypic expression of familial hypobetalipoproteinemia in three kindreds with mutations of apolipoprotein B gene J. Lipid Res., October 1, 2001; 42(10): 1552 - 1561. [Abstract] [Full Text] [PDF]

				N. Elias, B. W. Patterson, and G. Schonfeld Decreased Production Rates of VLDL Triglycerides and ApoB-100 in Subjects Heterozygous for Familial Hypobetalipoproteinemia Arterioscler. Thromb. Vasc. Biol., November 1, 1999; 19(11): 2714 - 2721. [Abstract] [Full Text] [PDF]

				Y. von Kodolitsch, R. E. Pyeritz, and P. K. Rogan Splice-Site Mutations in Atherosclerosis Candidate Genes : Relating Individual Information to Phenotype Circulation, August 17, 1999; 100(7): 693 - 699. [Abstract] [Full Text] [PDF]

				J. Wu, J. Kim, Q. Li, P.-Y. Kwok, T. G. Cole, B. Cefalu, M. Averna, and G. Schonfeld Known mutations of apoB account for only a small minority of hypobetalipoproteinemia J. Lipid Res., May 1, 1999; 40(5): 955 - 959. [Abstract] [Full Text]

				K. Ohashi, S. Ishibashi, M. Yamamoto, J.-i. Osuga, Y. Yazaki, S. Yukawa, and N. Yamada A Truncated Species of Apolipoprotein B (B-38.7) in a Patient With Homozygous Hypobetalipoproteinemia Associated With Diabetes Mellitus Arterioscler. Thromb. Vasc. Biol., August 1, 1998; 18(8): 1330 - 1334. [Abstract] [Full Text] [PDF]