|
Journal of Lipid Research, Vol 32, 1341-1348, Copyright © 1991 by Lipid Research, Inc.
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]
|
 |
|
Copyright © 1991 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|