Anderson's disease - Exclusion of apolipoprotein and intracellular lipid transport genes

被引:44
作者
Dannoura, AH
Berriot-Varoqueaux, N
Amati, P
Abadie, V
Verthier, N
Schmitz, J
Wetterau, JR
Samson-Bouma, ME
Aggerbeck, LP
机构
[1] Univ Paris 06, Ctr Genet Mol, CNRS, INSERM,U327,Fac Med Xavier Bichat, F-91198 Gif Sur Yvette, France
[2] Hop Necker Enfants Malad, INSERM, U393, Paris, France
[3] Hop Necker Enfants Malad, Dept Pediat, Paris, France
[4] Bristol Myers Squibb, Dept Metab Dis, Princeton, NJ USA
关键词
Anderson's disease; chylomicron retention disease hypocholesterolemia; apolipoprotein B; malabsorption;
D O I
10.1161/01.ATV.19.10.2494
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Anderson's disease is a rare, hereditary hypocholesterolemic syndrome characterized by chronic diarrhea, steatorrhea, and failure to thrive associated with the absence of apo B48-containing lipoproteins, To further define the molecular basis of the disease, we studied 8 affected subjects in 7 unrelated families of North African origin after treatment with a low-fat diet, Lipid loading of intestinal biopsies persisted, but the pattern and extent of loading was variable among the patients. Electron microscopy showed lipoprotein-like particles in membrane-bound compartments, the densities (0.65 to 7.5 particles/mu(2)) and the mean diameters (169 to 580 nm) of which were, in general, significantly larger than in a normal fed subject (0.66 particles/mu(2), 209 nm mean diameter). There were also large lipid particles having diameters up to 7043 nm (average diameters from 368 to 2127 nm) that were not surrounded by a membrane. Rarely, lipoprotein-like particles 50 to 150 nm in diameter were observed in the intercellular spaces. Intestinal organ culture showed that apo B and apo AIV were synthesized with apparently normal molecular weights and that small amounts were secreted in lipid-bound forms (density <1.006 g/mL). Normal microsomal triglyceride transfer protein (MTP) and activity were also detected in intestinal biopsies. Segregation analyses of 4 families excluded, as a cause of the disease, significant regions of the genome surrounding the genes for apo AI, ATV, B, CI, CII, CIII, and E, as were the genes encoding 3 proteins involved in intracellular lipid transport, MTP, and fatty acid binding proteins 1 and 2. The results suggest that a factor other than apoproteins and MTP are important for human intestinal chylomicron assembly and secretion.
引用
收藏
页码:2494 / 2508
页数:15
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