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

This Article Full Text 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 Tarugi, P. Articles by Calandra, S. Search for Related Content PubMed PubMed Citation Articles by Tarugi, P. Articles by Calandra, S. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 42, 1552-1561, October 2001
Copyright © 2001 by Lipid Research, Inc.

Original Article

Phenotypic expression of familial hypobetalipoproteinemia in three kindreds with mutations of apolipoprotein B gene

Correspondence to: Patrizia Tarugi, To whom correspondence should be addressed., tarugi{at}unimo.it (E-mail)

We report the clinical phenotype in three kindreds with familial heterozygous hypobetalipoproteinemia (FHBL) carrying novel truncated apolipoprotein Bs (apoBs) of different sizes (apoB-8.15, apoB-33.4 and apoB-75.7). In D.A. kindred, we found three carriers of a C-deletion in exon 10 leading to the synthesis of apoB-8.15 not detectable in plasma. They showed steatorrhea and fatty liver. In N.L. kindred, the proband is heterozygous for a nonsense mutation in exon 26, leading to the formation of apoB-33.4. He had premature cerebrovascular disease and fatty liver; two apoB-33.4 carriers in this kindred showed only fatty liver. In B.E. kindred, the proband is heterozygous for a T-deletion in exon 26, which converts tyrosine at codon 3435 into a stop codon, resulting in apoB-75.7. The proband, a heavy alcohol drinker, had steatohepatitis, whereas his teetotaller daughter, an apoB-75.7 carrier, had no detectable fatty liver.

This study suggests that: i) fatty liver invariably develops in FHBL carriers of short and medium-size truncated apoBs (< apoB-48), but its occurrence needs additional environmental factors in carriers of longer apoB forms; ii) intestinal lipid malabsorption develops only in carriers of short truncated apoBs, which are not secreted into the plasma; and iii) cerebrovascular disease due to premature atherosclerosis may occur even in FHBL subjects. — Tarugi, P., 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. 2001. 42: 1552–1561.

Supplementary key words: truncated apoBs, fatty liver, lipid malabsorption, carotid atherosclerosis

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

This article has been cited by other articles:

				T. Fasano, A. B. Cefalu, E. Di Leo, D. Noto, D. Pollaccia, L. Bocchi, V. Valenti, R. Bonardi, O. Guardamagna, M. Averna, et al. A Novel Loss of Function Mutation of PCSK9 Gene in White Subjects With Low-Plasma Low-Density Lipoprotein Cholesterol Arterioscler. Thromb. Vasc. Biol., March 1, 2007; 27(3): 677 - 681. [Abstract] [Full Text] [PDF]

				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]

				J. J.P. Kastelein, M. K. Wedel, B. F. Baker, J. Su, J. D. Bradley, R. Z. Yu, E. Chuang, M. J. Graham, and R. M. Crooke Potent Reduction of Apolipoprotein B and Low-Density Lipoprotein Cholesterol by Short-Term Administration of an Antisense Inhibitor of Apolipoprotein B Circulation, October 17, 2006; 114(16): 1729 - 1735. [Abstract] [Full Text] [PDF]

				R. M. Crooke, M. J. Graham, K. M. Lemonidis, C. P. Whipple, S. Koo, and R. J. Perera An apolipoprotein B antisense oligonucleotide lowers LDL cholesterol in hyperlipidemic mice without causing hepatic steatosis J. Lipid Res., May 1, 2005; 46(5): 872 - 884. [Abstract] [Full Text] [PDF]

				S W Fouchier, R R Sankatsing, J Peter, S Castillo, M Pocovi, R Alonso, J J P Kastelein, and J C Defesche High frequency of APOB gene mutations causing familial hypobetalipoproteinaemia in patients of Dutch and Spanish descent J. Med. Genet., April 1, 2005; 42(4): e23 - e23. [Abstract] [Full Text] [PDF]

				T. Tanoli, P. Yue, D. Yablonskiy, and G. Schonfeld Fatty liver in familial hypobetalipoproteinemia: roles of the APOB defects, intra-abdominal adipose tissue, and insulin sensitivity J. Lipid Res., May 1, 2004; 45(5): 941 - 947. [Abstract] [Full Text] [PDF]

				Z. Chen, R. L. Fitzgerald, G. Li, N. O. Davidson, and G. Schonfeld Hepatic secretion of apoB-100 is impaired in hypobetalipoproteinemic mice with an apoB-38.9-specifying allele J. Lipid Res., January 1, 2004; 45(1): 155 - 163. [Abstract] [Full Text] [PDF]

				G. Schonfeld Familial hypobetalipoproteinemia: a review J. Lipid Res., May 1, 2003; 44(5): 878 - 883. [Abstract] [Full Text] [PDF]

				J. R. Burnett, J. Shan, B. A. Miskie, A. J. Whitfield, J. Yuan, K. Tran, C. J. McKnight, R. A. Hegele, and Z. Yao A Novel Nontruncating APOB Gene Mutation, R463W, Causes Familial Hypobetalipoproteinemia J. Biol. Chem., April 4, 2003; 278(15): 13442 - 13452. [Abstract] [Full Text] [PDF]

				Z. Chen, R. L. Fitzgerald, J. E. Saffitz, C. F. Semenkovich, and G. Schonfeld Amino Terminal 38.9% of Apolipoprotein B-100 Is Sufficient to Support Cholesterol-Rich Lipoprotein Production and Atherosclerosis Arterioscler. Thromb. Vasc. Biol., April 1, 2003; 23(4): 668 - 674. [Abstract] [Full Text] [PDF]

				G. Schonfeld, B. W. Patterson, D. A. Yablonskiy, T. S. K. Tanoli, M. Averna, N. Elias, P. Yue, and J. Ackerman Fatty liver in familial hypobetalipoproteinemia: triglyceride assembly into VLDL particles is affected by the extent of hepatic steatosis J. Lipid Res., March 1, 2003; 44(3): 470 - 478. [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]