title: Homozygosity for the transthyretin-met30-gene in two Swedish sibs with familial amyloidotic polyneuropathy.
abstract: Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant inherited disorder. Recent biochemical studies have revealed that amyloid protein in FAP of Japanese, Swedish and Portuguese origin mainly consists of a variant transthyretin (TTR) (formerly called prealbumin) with one amino acid substitution of methionine for valine at position 30. In a 56-year-old man with typical polyneuropathy, gastrointestinal problems and vitreous amyloid, we diagnosed homozygosity for the TTR-met30-gene using RFLP analysis. In a family study, a sister presented the same homozygous RFLP pattern; however, in a careful clinical investigation we were not able to demonstrate any of the typical symptoms of FAP, nor could we demonstrate amyloid deposits in a biopsy skin specimen. This is the first report of homozygosity for the TTR-met30-gene, and it shows that the mutation of the protein involved in amyloid formation may be necessary but is clearly not sufficient for the clinical symptoms.
authors.affiliation: Department of Clinical Genetics, University Hospital, Umeå, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Holmgren
authors.forename: E
authors.initials: E
authors.lastname: Haettner
authors.forename: I
authors.initials: I
authors.lastname: Nordenson
authors.forename: O
authors.initials: O
authors.lastname: Sandgren
authors.forename: L
authors.initials: L
authors.lastname: Steen
authors.forename: E
authors.initials: E
authors.lastname: Lundgren
mesh_terms: D000328:Adult; D000686:Amyloidosis / Q000235:genetics*; D005260:Female; D009477:Hereditary Sensory and Autonomic Neuropathies / Q000235:genetics*; D015417:Hereditary Sensory and Motor Neuropathy / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D011228:Prealbumin / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D013548:Sweden
chemical_list: D011228:Prealbumin; D008715:Methionine