Four new mutations in the apolipoprotein B gene causing hypobetalipoproteinemia, including two different frameshift mutations that yield truncated apolipoprotein B proteins of identical length

S. G. Young, C. R. Pullinger, B. R. Zysow, H. Hofmann-Radvani, M. F. Linton, R. V. Farese, J. F. Terdiman, S. M. Snyder, Scott M Grundy, Gloria L Vega, M. J. Malloy, J. P. Kane

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Familial hypobetalipoproteinemia can be caused by mutations in the apolipoprotein (apo)B gene that interfere with the translation of a full- length apoB molecule. Frequently, a truncated apoB molecule can be detected in the plasma lipoproteins of affected subjects. In this report, we characterize four different apoB gene mutations causing hypobetalipoproteinemia that are associated with the synthesis of truncated apoB proteins. Two of the mutations are nonsense mutations caused by single nucleotide substitutions; these mutations are associated with the production of apoB-32.5 (1473 amino acids) and apoB-82 (3733 amino acids). The other two mutations are single nucleotide deletions (of apoB cDNA nucleotides 7295 and 7359, respectively). The altered reading frames created by these different frameshift mutations terminated with the same stop codon, and both therefore yielded a truncated protein of identical size: apoB-52.8 (2395 amino acids). The two apoB-52.8 proteins differ, however, in the number of novel carboxyl- terminal amino acids introduced by the frameshift. The buoyant density of lipoproteins containing the truncated apoBs was inversely related to the length of the truncated apoB. ApoB-32.5 was present only in high density lipoproteins (HDL) and the d > 1.21 g/ml fraction, whereas apoB-82 was present almost exclusively in very low density lipoproteins (VLDL). ApoB- 52.8 was present primarily in VLDL, intermediate density lipoproteins (IDL), and low density lipoproteins (LDL); trace amounts were observed in the HDL.

Original languageEnglish (US)
Pages (from-to)501-507
Number of pages7
JournalJournal of Lipid Research
Volume34
Issue number3
StatePublished - 1993

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Hypobetalipoproteinemias
Frameshift Mutation
Apolipoproteins B
Genes
Mutation
Proteins
Amino Acids
Nucleotides
VLDL Lipoproteins
HDL Lipoproteins
Lipoproteins
IDL Lipoproteins
Reading Frames
Molecules
Terminator Codon
Nonsense Codon

Keywords

  • HDL
  • IDL
  • LDL
  • VLDL

ASJC Scopus subject areas

  • Endocrinology

Cite this

Four new mutations in the apolipoprotein B gene causing hypobetalipoproteinemia, including two different frameshift mutations that yield truncated apolipoprotein B proteins of identical length. / Young, S. G.; Pullinger, C. R.; Zysow, B. R.; Hofmann-Radvani, H.; Linton, M. F.; Farese, R. V.; Terdiman, J. F.; Snyder, S. M.; Grundy, Scott M; Vega, Gloria L; Malloy, M. J.; Kane, J. P.

In: Journal of Lipid Research, Vol. 34, No. 3, 1993, p. 501-507.

Research output: Contribution to journalArticle

Young, SG, Pullinger, CR, Zysow, BR, Hofmann-Radvani, H, Linton, MF, Farese, RV, Terdiman, JF, Snyder, SM, Grundy, SM, Vega, GL, Malloy, MJ & Kane, JP 1993, 'Four new mutations in the apolipoprotein B gene causing hypobetalipoproteinemia, including two different frameshift mutations that yield truncated apolipoprotein B proteins of identical length', Journal of Lipid Research, vol. 34, no. 3, pp. 501-507.
Young, S. G. ; Pullinger, C. R. ; Zysow, B. R. ; Hofmann-Radvani, H. ; Linton, M. F. ; Farese, R. V. ; Terdiman, J. F. ; Snyder, S. M. ; Grundy, Scott M ; Vega, Gloria L ; Malloy, M. J. ; Kane, J. P. / Four new mutations in the apolipoprotein B gene causing hypobetalipoproteinemia, including two different frameshift mutations that yield truncated apolipoprotein B proteins of identical length. In: Journal of Lipid Research. 1993 ; Vol. 34, No. 3. pp. 501-507.
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abstract = "Familial hypobetalipoproteinemia can be caused by mutations in the apolipoprotein (apo)B gene that interfere with the translation of a full- length apoB molecule. Frequently, a truncated apoB molecule can be detected in the plasma lipoproteins of affected subjects. In this report, we characterize four different apoB gene mutations causing hypobetalipoproteinemia that are associated with the synthesis of truncated apoB proteins. Two of the mutations are nonsense mutations caused by single nucleotide substitutions; these mutations are associated with the production of apoB-32.5 (1473 amino acids) and apoB-82 (3733 amino acids). The other two mutations are single nucleotide deletions (of apoB cDNA nucleotides 7295 and 7359, respectively). The altered reading frames created by these different frameshift mutations terminated with the same stop codon, and both therefore yielded a truncated protein of identical size: apoB-52.8 (2395 amino acids). The two apoB-52.8 proteins differ, however, in the number of novel carboxyl- terminal amino acids introduced by the frameshift. The buoyant density of lipoproteins containing the truncated apoBs was inversely related to the length of the truncated apoB. ApoB-32.5 was present only in high density lipoproteins (HDL) and the d > 1.21 g/ml fraction, whereas apoB-82 was present almost exclusively in very low density lipoproteins (VLDL). ApoB- 52.8 was present primarily in VLDL, intermediate density lipoproteins (IDL), and low density lipoproteins (LDL); trace amounts were observed in the HDL.",
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T1 - Four new mutations in the apolipoprotein B gene causing hypobetalipoproteinemia, including two different frameshift mutations that yield truncated apolipoprotein B proteins of identical length

AU - Young, S. G.

AU - Pullinger, C. R.

AU - Zysow, B. R.

AU - Hofmann-Radvani, H.

AU - Linton, M. F.

AU - Farese, R. V.

AU - Terdiman, J. F.

AU - Snyder, S. M.

AU - Grundy, Scott M

AU - Vega, Gloria L

AU - Malloy, M. J.

AU - Kane, J. P.

PY - 1993

Y1 - 1993

N2 - Familial hypobetalipoproteinemia can be caused by mutations in the apolipoprotein (apo)B gene that interfere with the translation of a full- length apoB molecule. Frequently, a truncated apoB molecule can be detected in the plasma lipoproteins of affected subjects. In this report, we characterize four different apoB gene mutations causing hypobetalipoproteinemia that are associated with the synthesis of truncated apoB proteins. Two of the mutations are nonsense mutations caused by single nucleotide substitutions; these mutations are associated with the production of apoB-32.5 (1473 amino acids) and apoB-82 (3733 amino acids). The other two mutations are single nucleotide deletions (of apoB cDNA nucleotides 7295 and 7359, respectively). The altered reading frames created by these different frameshift mutations terminated with the same stop codon, and both therefore yielded a truncated protein of identical size: apoB-52.8 (2395 amino acids). The two apoB-52.8 proteins differ, however, in the number of novel carboxyl- terminal amino acids introduced by the frameshift. The buoyant density of lipoproteins containing the truncated apoBs was inversely related to the length of the truncated apoB. ApoB-32.5 was present only in high density lipoproteins (HDL) and the d > 1.21 g/ml fraction, whereas apoB-82 was present almost exclusively in very low density lipoproteins (VLDL). ApoB- 52.8 was present primarily in VLDL, intermediate density lipoproteins (IDL), and low density lipoproteins (LDL); trace amounts were observed in the HDL.

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KW - HDL

KW - IDL

KW - LDL

KW - VLDL

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