Mutations in MTP gene in abeta- and hypobeta-lipoproteinemia

被引:47
作者
Di Leo, E
Lancellotti, S
Penacchioni, JY
Cefalù, AB
Averna, M
Pisciotta, L
Bertolini, S
Calandra, S
Gabelli, C
Tarugi, P
机构
[1] Univ Modena & Reggio Emilia, Dept Biomed Sci, I-41100 Modena, Italy
[2] Univ Genoa, Dept Internal Med, I-16132 Genoa, Italy
[3] Dept Internal Med, I-90127 Palermo, Italy
[4] Univ Padua, Azienda Osped, I-35128 Padua, Italy
关键词
abetalipoproteinemia; hypobetalipoproteinemia; MTP gene; apo B gene; gene mutations; apo E genotype;
D O I
10.1016/j.athersclerosis.2004.12.004
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Familial hypobetalipoproteinemia (FHBL) and abetalipoproteinemia (ABL) are inherited disorders of apolipoprotein B (apo B)-containing lipoproteins that result from mutations in apo B and microsomal triglyceride transfer protein (MTP) genes, respectively. Here we report three patients with severe deficiency of plasma low-density lipoprotein (LDL) and apo B. Two of them (probands F.A. and P.E.) had clinical and biochemical phenotype consistent with ABL. Proband F.A. was homozygous for a minute deletion/insertion (c. 1228delCCCinsT) in exon 9 of MTP gene predicted to cause a truncated MTP protein of 412 amino acids. Proband R E. was heterozygous for a mutation in intron 9 (IVS9-1G > A), previously reported in an ABL patient. We failed to find the second pathogenic mutation in MTP gene of this patient. No mutations were found in apo B gene. The third proband (D.F.) had a less severe lipoprotein phenotype which was similar to that of heterozygous FHBL and appeared to be inherited as a co-dominant trait. However, he had no mutations in apo B gene. He was found to be a compound heterozygote for two missense mutations (D384A and G661 A), involving highly conserved regions of MTP. Since this proband was also homozygous for 82 allele of apolipoprotein E (apo E), it is likely that his hypobetalipoproteinemia derives from a combined effect of a mild MTP deficiency and homozygosity for apo E2 isoform. (c) 2004 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:311 / 318
页数:8
相关论文
共 22 条
[11]  
NARCISI TME, 1995, AM J HUM GENET, V57, P1298
[12]  
Ohashi K, 2000, J LIPID RES, V41, P1199
[13]   A novel abetalipoproteinemia genotype - Identification of a missense mutation in the 97-kDa subunit of the microsomal triglyceride transfer protein that prevents complex formation with protein disulfide isomerase [J].
Rehberg, EF ;
SamsonBouma, ME ;
Kienzle, B ;
Blinderman, L ;
Jamil, H ;
Wetterau, JR ;
Aggerbeck, LP ;
Gordon, DA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (47) :29945-29952
[14]   A 30-AMINO ACID TRUNCATION OF THE MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN LARGE SUBUNIT DISRUPTS ITS INTERACTION WITH PROTEIN DISULFIDE-ISOMERASE AND CAUSES ABETALIPOPROTEINEMIA [J].
RICCI, B ;
SHARP, D ;
OROURKE, E ;
KIENZLE, B ;
BLINDERMAN, L ;
GORDON, D ;
SMITHMONROY, C ;
ROBINSON, G ;
GREGG, RE ;
RADER, DJ ;
WETTERAU, JR .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (24) :14281-14285
[15]   Familial hypobetalipoproteinemia: a review [J].
Schonfeld, G .
JOURNAL OF LIPID RESEARCH, 2003, 44 (05) :878-883
[16]   CLONING AND GENE DEFECTS IN MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN ASSOCIATED WITH ABETALIPOPROTEINEMIA [J].
SHARP, D ;
BLINDERMAN, L ;
COMBS, KA ;
KIENZLE, B ;
RICCI, B ;
WAGERSMITH, K ;
GIL, CM ;
TURCK, CW ;
BOUMA, ME ;
RADER, DJ ;
AGGERBECK, LP ;
GREGG, RE ;
GORDON, DA ;
WETTERAU, JR .
NATURE, 1993, 365 (6441) :65-69
[17]   ABETALIPOPROTEINEMIA IS CAUSED BY DEFECTS OF THE GENE ENCODING THE 97 KDA SUBUNIT OF A MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN [J].
SHOULDERS, CC ;
BRETT, DJ ;
BAYLISS, JD ;
NARCISI, TME ;
JARMUZ, A ;
GRANTHAM, TT ;
LEONI, PRD ;
BHATTACHARYA, S ;
PEASE, RJ ;
CULLEN, PM ;
LEVI, S ;
BYFIELD, PGH ;
PURKISS, P ;
SCOTT, J .
HUMAN MOLECULAR GENETICS, 1993, 2 (12) :2109-2116
[18]  
Tarugi P, 2001, J LIPID RES, V42, P1552
[19]   APOLIPOPROTEIN-E POLYMORPHISM IN HEALTH AND DISEASE [J].
UTERMANN, G .
AMERICAN HEART JOURNAL, 1987, 113 (02) :433-440
[20]  
Wang J, 2000, Hum Mutat, V15, P294, DOI 10.1002/(SICI)1098-1004(200003)15:3<294::AID-HUMU14>3.0.CO