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Structure of the mutant prealbumin gene responsible for familial amyloidotic polyneuropathy
Abstract:
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.
Insights
Familial amyloidotic polyneuropathy (FAP) is a genetic disorder. Researchers identified the specific prealbumin gene mutation causing the Val30Met change in FAP patients, distinguishing it from other genetic variations.
Area of Science:
- Genetics
- Molecular Biology
- Neurology
Background:
- Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant genetic disorder.
- Amyloid fibrils in FAP patients contain a prealbumin variant (Val30Met substitution).
- The specific prealbumin gene structure causing this variation was previously uncharacterized.
Purpose of the Study:
- To determine the complete nucleotide sequence of the prealbumin gene in a Japanese FAP patient.
- To characterize the genetic basis of the Val30Met substitution in FAP.
Main Methods:
- Determined the complete nucleotide sequence of the prealbumin gene from an FAP patient.
- Compared the patient's gene sequence with a normal prealbumin gene sequence.
- Utilized hybridization analyses of normal and FAP patient DNAs.
Main Results:
- The FAP patient's prealbumin gene had seven base substitutions compared to the normal gene.
- The Val30Met substitution was located in exon 2.
- Other substitutions were found in introns and identified as polymorphic changes.
- The exon 2 substitution was specific to FAP, while intronic changes were not.
Conclusions:
- The mutation responsible for the Val30Met change is the sole base change specific to FAP within the prealbumin gene.
- This specific mutation in the prealbumin gene is the cause of familial amyloidotic polyneuropathy.