title: Novel mutations in the microsomal triglyceride transfer protein gene causing abetalipoproteinemia.
abstract: 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.
authors.affiliation: Department of Metabolic Diseases, Faculty of Medicine, University of Tokyo, Tokyo, 113-8655, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ohashi
authors.forename: S
authors.initials: S
authors.lastname: Ishibashi
authors.forename: J
authors.initials: J
authors.lastname: Osuga
authors.forename: R
authors.initials: R
authors.lastname: Tozawa
authors.forename: K
authors.initials: K
authors.lastname: Harada
authors.forename: N
authors.initials: N
authors.lastname: Yahagi
authors.forename: F
authors.initials: F
authors.lastname: Shionoiri
authors.forename: Y
authors.initials: Y
authors.lastname: Iizuka
authors.forename: Y
authors.initials: Y
authors.lastname: Tamura
authors.forename: R
authors.initials: R
authors.lastname: Nagai
authors.forename: D R
authors.initials: DR
authors.lastname: Illingworth
authors.forename: T
authors.initials: T
authors.lastname: Gotoda
authors.forename: N
authors.initials: N
authors.lastname: Yamada
mesh_terms: D000012:Abetalipoproteinemia / Q000235:genetics*; D000225:Adenine; D000293:Adolescent; D000328:Adult; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D018076:DNA, Complementary / Q000737:chemistry; D005260:Female; D016368:Frameshift Mutation; D015870:Gene Expression; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D017422:Sequence Analysis, DNA; D014162:Transfection
chemical_list: D002352:Carrier Proteins; D018076:DNA, Complementary; C106092:microsomal triglyceride transfer protein; D000225:Adenine