Novel mutations in the microsomal triglyceride transfer protein gene causing abetalipoproteinemia
Abetalipoproteinemia (ABL) is an inherited disease characterized by the virtual absence of apolipoprotein B (apoB)-containing lipoproteins from plasma. Only limited numbers of families have been screened for mutations in the microsomal triglyceride transfer protein (MTP) gene. To clarify the genetic...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2000-08-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S002222752033426X |
| _version_ | 1818384683222695936 |
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| author | Ken Ohashi Shun Ishibashi Jun-ichi Osuga Ryu-ichi Tozawa Kenji Harada Naoya Yahagi Futoshi Shionoiri Yoko Iizuka Yoshiaki Tamura Ryozo Nagai D. Roger Illingworth Takanari Gotoda Nobuhiro Yamada |
| author_facet | Ken Ohashi Shun Ishibashi Jun-ichi Osuga Ryu-ichi Tozawa Kenji Harada Naoya Yahagi Futoshi Shionoiri Yoko Iizuka Yoshiaki Tamura Ryozo Nagai D. Roger Illingworth Takanari Gotoda Nobuhiro Yamada |
| author_sort | Ken Ohashi |
| collection | DOAJ |
| description | Abetalipoproteinemia (ABL) is an inherited disease characterized by the virtual absence of apolipoprotein B (apoB)-containing lipoproteins from plasma. Only limited numbers of families have been screened for mutations in the microsomal triglyceride transfer protein (MTP) gene. To clarify the genetic basis of clinical diversity of ABL, mutations of the MTP gene have been screened in 4 unrelated patients with ABL. Three novel mutations have been identified: a frameshift mutation caused by a single adenine deletion at position 1389 of the cDNA, and a missense mutation, Asn780Tyr, each in homozygous forms; and a splice site mutation, 2218-2A→G, in a compound heterozygous form. The frameshift and splice site mutations are predicted to encode truncated forms of MTP. When transiently expressed in Cos-1 cells, the Asn780Tyr mutant MTP bound protein disulfide isomerase (PDI) but displayed negligible MTP activity. It is of interest that the patient having the Asn780Tyr mutation, a 27-year-old male, has none of the manifestations characteristic of classic ABL even though his plasma apoB and vitamin E were virtually undetectable. These results indicated that defects of the MTP gene are the proximal cause of ABL. —Ohashi, K., S. Ishibashi, J-i. Osuga, R-i. Tozawa, K. Harada, N. Yahagi, F. Shionoiri, Y. Iizuka, Y. Tamura, R. Nagai, D. R. Illingworth, T. Gotoda, and N. Yamada. Novel mutations in the microsomal triglyceride transfer protein gene causing abetalipoproteinemia. J. Lipid Res. 2000. 41: 1199–1204. |
| first_indexed | 2024-12-14T03:26:09Z |
| format | Article |
| id | doaj.art-8abf54d00e43433bab0e2de5a8116070 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-14T03:26:09Z |
| publishDate | 2000-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-8abf54d00e43433bab0e2de5a81160702022-12-21T23:18:52ZengElsevierJournal of Lipid Research0022-22752000-08-0141811991204Novel mutations in the microsomal triglyceride transfer protein gene causing abetalipoproteinemiaKen Ohashi0Shun Ishibashi1Jun-ichi Osuga2Ryu-ichi Tozawa3Kenji Harada4Naoya Yahagi5Futoshi Shionoiri6Yoko Iizuka7Yoshiaki Tamura8Ryozo Nagai9D. Roger Illingworth10Takanari Gotoda11Nobuhiro Yamada12Department of Metabolic Diseases, Faculty of Medicine, University of Tokyo, Tokyo, 113-8655, JapanDepartment of Metabolic Diseases, Faculty of Medicine, University of Tokyo, Tokyo, 113-8655, Japan; To whom correspondence should be addressed.Department of Metabolic Diseases, Faculty of Medicine, University of Tokyo, Tokyo, 113-8655, JapanDepartment of Metabolic Diseases, Faculty of Medicine, University of Tokyo, Tokyo, 113-8655, JapanDepartment of Metabolic Diseases, Faculty of Medicine, University of Tokyo, Tokyo, 113-8655, JapanDepartment of Metabolic Diseases, Faculty of Medicine, University of Tokyo, Tokyo, 113-8655, JapanDepartment of Metabolic Diseases, Faculty of Medicine, University of Tokyo, Tokyo, 113-8655, JapanDepartment of Metabolic Diseases, Faculty of Medicine, University of Tokyo, Tokyo, 113-8655, JapanDepartment of Metabolic Diseases, Faculty of Medicine, University of Tokyo, Tokyo, 113-8655, JapanDepartment of Cardiology, Faculty of Medicine, University of Tokyo, Tokyo, 113-8655, JapanDepartment of Medicine, Division of Endocrinology, Diabetes, and Clinical Nutrition, Oregon Health Sciences University, Portland, OR 97201Department of Metabolic Diseases, Faculty of Medicine, University of Tokyo, Tokyo, 113-8655, JapanDepartment of Endocrinology, Metabolism, and Atherosclerosis, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan 305-8575Abetalipoproteinemia (ABL) is an inherited disease characterized by the virtual absence of apolipoprotein B (apoB)-containing lipoproteins from plasma. Only limited numbers of families have been screened for mutations in the microsomal triglyceride transfer protein (MTP) gene. To clarify the genetic basis of clinical diversity of ABL, mutations of the MTP gene have been screened in 4 unrelated patients with ABL. Three novel mutations have been identified: a frameshift mutation caused by a single adenine deletion at position 1389 of the cDNA, and a missense mutation, Asn780Tyr, each in homozygous forms; and a splice site mutation, 2218-2A→G, in a compound heterozygous form. The frameshift and splice site mutations are predicted to encode truncated forms of MTP. When transiently expressed in Cos-1 cells, the Asn780Tyr mutant MTP bound protein disulfide isomerase (PDI) but displayed negligible MTP activity. It is of interest that the patient having the Asn780Tyr mutation, a 27-year-old male, has none of the manifestations characteristic of classic ABL even though his plasma apoB and vitamin E were virtually undetectable. These results indicated that defects of the MTP gene are the proximal cause of ABL. —Ohashi, K., S. Ishibashi, J-i. Osuga, R-i. Tozawa, K. Harada, N. Yahagi, F. Shionoiri, Y. Iizuka, Y. Tamura, R. Nagai, D. R. Illingworth, T. Gotoda, and N. Yamada. Novel mutations in the microsomal triglyceride transfer protein gene causing abetalipoproteinemia. J. Lipid Res. 2000. 41: 1199–1204.http://www.sciencedirect.com/science/article/pii/S002222752033426Xmicrosomal triglyceride transfer proteinabetalipoproteinemiaapolipoprotein Btriglyceridescholesterollipoproteins |
| spellingShingle | Ken Ohashi Shun Ishibashi Jun-ichi Osuga Ryu-ichi Tozawa Kenji Harada Naoya Yahagi Futoshi Shionoiri Yoko Iizuka Yoshiaki Tamura Ryozo Nagai D. Roger Illingworth Takanari Gotoda Nobuhiro Yamada Novel mutations in the microsomal triglyceride transfer protein gene causing abetalipoproteinemia Journal of Lipid Research microsomal triglyceride transfer protein abetalipoproteinemia apolipoprotein B triglycerides cholesterol lipoproteins |
| title | Novel mutations in the microsomal triglyceride transfer protein gene causing abetalipoproteinemia |
| title_full | Novel mutations in the microsomal triglyceride transfer protein gene causing abetalipoproteinemia |
| title_fullStr | Novel mutations in the microsomal triglyceride transfer protein gene causing abetalipoproteinemia |
| title_full_unstemmed | Novel mutations in the microsomal triglyceride transfer protein gene causing abetalipoproteinemia |
| title_short | Novel mutations in the microsomal triglyceride transfer protein gene causing abetalipoproteinemia |
| title_sort | novel mutations in the microsomal triglyceride transfer protein gene causing abetalipoproteinemia |
| topic | microsomal triglyceride transfer protein abetalipoproteinemia apolipoprotein B triglycerides cholesterol lipoproteins |
| url | http://www.sciencedirect.com/science/article/pii/S002222752033426X |
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