Biochemical and molecular genetic characterization of a new variant prealbumin associated with hereditary amyloidosis

M. R. Wallace, F. E. Dwulet, P. M. Conneally, Merrill Benson

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Abstract

Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant late-onset disorder characterized by the extracellular deposition of amyloid fibrils. In all cases studied these fibrils have been found to be composed of plasma prealbumin (transthyretin) containing a single amino acid substitution. Biochemical studies were conducted on amyloid from one patient and plasma prealbumin from his affected brother, both part of a large kindred from the Appalachian region of the United States. Sequence analysis of the amyloid subunit protein showed it to be prealbumin with about two-thirds of the molecules containing a substitution of alanine for threonine at position 60. Studies of the plasma prealbumin showed that the same substitution was present in 40-45% of the protein. Based on this substitution and the prealbumin cDNA sequence, a Pvu II restriction fragment length DNA polymorphism (RFLP) was predicted and demonstrated in DNA of both patients as well as other family members. This RFLP confirms the predicted DNA mutation responsible for the protein variant, and represents an accurate method for detection of this gene.

Original languageEnglish
Pages (from-to)6-12
Number of pages7
JournalJournal of Clinical Investigation
Volume78
Issue number1
StatePublished - 1986

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Familial Amyloidosis
Prealbumin
Molecular Biology
DNA
Amyloid
Restriction Fragment Length Polymorphisms
Appalachian Region
Amyloidogenic Proteins
Polyneuropathies
Threonine
Amino Acid Substitution
Alanine
Sequence Analysis
Siblings
Proteins
Complementary DNA
Mutation
Genes

ASJC Scopus subject areas

  • Medicine(all)

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Biochemical and molecular genetic characterization of a new variant prealbumin associated with hereditary amyloidosis. / Wallace, M. R.; Dwulet, F. E.; Conneally, P. M.; Benson, Merrill.

In: Journal of Clinical Investigation, Vol. 78, No. 1, 1986, p. 6-12.

Research output: Contribution to journalArticle

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