Structure of the mutant prealbumin gene responsible for familial amyloidotic polyneuropathy.
Familial amyloidotic polyneuropathy (FAP) is a genetic disorder showing autosomal dominant inheritance. Amyloid fibrils of FAP patients from various origins have been shown to contain a prealbumin variant with Val30----Met30 substitution as a major component. However, the structure of the prealbumin gene responsible for the variation has not been characterized. We determined the complete nucleotide sequence of the prealbumin gene from a patient with the Japanese type of FAP. In comparison with a normal prealbumin gene sequence, the patient's gene was found to be carrying seven base substitutions. The substitution responsible for the Val----Met change was found in exon 2, as expected, and the others were in introns. Hybridization analyses of normal and FAP patient DNAs showed that the base substitution in exon 2 was specific for FAP but the others were polymorphic changes. It was concluded that the mutation responsible for the Val----Met change is the only base change specific for FAP in the prealbumin gene.
D000686:Amyloidosis / Q000235:genetics*; D001483:Base Sequence; D003001:Cloning, Molecular; D004262:DNA Restriction Enzymes; D005796:Genes; D006801:Humans; D009154:Mutation; D009422:Nervous System Diseases / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D011110:Polymorphism, Genetic; D011228:Prealbumin / Q000235:genetics*
D011228:Prealbumin; D004262:DNA Restriction Enzymes