Independent mutation of arginine(3500)-->glutamine associated with familial defective apolipoprotein B-100.
Familial defective apolipoprotein B-100 (FDB) is characterized by a decreased affinity of low density lipoprotein (LDL) to the LDL receptor resulting in a dominantly inherited increase of plasma LDL. It is postulated that FDB is caused by a G to A mutation at nucleotide 10,708 in exon 26 of the apoB gene creating a substitution of glutamine for arginine in amino acid 3500. The arginine(3500)-->glutamine mutation has been identified on the same haplotype of the apoB gene in several populations from North America and Europe, suggesting that it occurred on a single ancestral gene. Independent mutations were not observed. The purpose of this paper is to report on a family where individuals show a dominantly inherited increase of plasma LDL associated with an independent arginine(3500)-->glutamine mutation as determined by haplotype analysis using polymorphic markers of the apoB gene. The identification of these individuals is strong evidence that the arginine(3500)-->glutamine mutation is causative for the defective binding of apoB-100.
Medizinische Poliklinik der Universität, München, Germany.
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G
Rauh
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H
Schuster
C K
CK
Schewe
G
G
Stratmann
C
C
Keller
G
G
Wolfram
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N
Zöllner
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000235:genetics* / Q000378:metabolism; D001120:Arginine / Q000235:genetics; D001483:Base Sequence; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D005819:Genetic Markers; D005858:Germany / Q000208:ethnology; D005973:Glutamine / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D013329:Structure-Activity Relationship
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D005819:Genetic Markers; D008077:Lipoproteins, LDL; D005973:Glutamine; D001120:Arginine