Summary
Transthyretin methionine 30 (TTR Met 30), which is associated with familial amyloidotic polyneuropathy, originates in a single base substitution (A for G) in the second exon of the TTR gene. This autosomal dominant disease can be diagnosed by RFLP analysis of NsiI-digested DNA. The amplification of DNA by PCR improves the diagnosis method, making it suitable for prenatal diagnosis. Using PCR-amplified DNA, prenatal diagnosis of two at-risk fetuses was performed. Control Met 30 and normal DNA (either genomic or produced by site directed mutagenesis) were processed in parallel. The diagnosis was made by hybridization with allele-specific oligonucleotide probes, and later confirmed by screening of the mutant protein in the amniotic fluid and, when possible, in the sera from the newborns. TTR Met 30 was detected in the amniotic fluid of a positive fetus whose father was the carrier of the mutation. This indicates that the mutant protein is expressed very early in development.
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References
Benson MD, Dwulet FE (1985) Identification of carriers of a variant plasma prealbumin (transthyretin) associated with familial amyloidotic polyneuropathy. J Clin Invest 75:71–75
Costa PP, Figueira A, Bravo F (1978) Amyloid fibril protein related to prealbumin in familial amyloidotic polyneuropathy. Proc Natl Acad Sci USA 75:4499–4503
Furuya H, Nakazato M, Saraiva MJM, Costa PP, Sasaki H, Matsuo H, Goto I, Sakaki Y (1989) Tetramer formation of variant type human transthyretin (prealbumin) produced by Escherichia coli expression vector. Biochem Biophys Res Commun 163:851–859
Gitlin D, Gitlin JD (1975) Fetal and neonatal development of human plasma proteins. In: Putnam FW (ed) The plasma proteins, vol II, 2nd edn. Academic Press, New York London, 264–371
Jacobsson B (1989) Localization of transthyretin-mRNA and of immunoreactive transthyretin in the human fetus. Virchows Arch [A] 415:259–263
Kan YW, Dozy AM (1978) Polymorphisms of DNA sequence adjacent to human β-globin structural gene: relationship to sickle mutation. Proc Natl Acad Sci USA 75:5631–5635
Nakazato M, Kurihara T, Matsukura S, Kangawa K, Matsuo H, (1986) Diagnostic radioimmunoassay for familial amyloidotic polyneuropathy before clinical onset. J Clin Invest 77:1699–1703
Saiki RK, Scharf S, Faloona F, Mullis KB, Horn GT, Erlich HA, Arnheim N (1985) Enzymatic amplification of β-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 230:1350–1354
Saraiva MJM, Costa PP, Birken S, Goodman DS (1983) Presence of an abnormal transthyretin (prealbumin) in familial amyloidotic polyneuropathy, Portuguese type. Trans Assoc Am Physicians 96:261–270
Saraiva MJM, Birken S, Costa PP, Goodman DS (1984) Amyloid fibril protein in familial amyloidotic polyneuropathy, Portuguese type. Definition of molecular abnormality in transthyretin (prealbumin). J Clin Invest 74:104–119
Saraiva MJM, Costa PP, Goodman DS (1985a) Biochemical marker in familial amyloidotic polyneuropathy, Portuguese type. J Clin Invest 76:2171–2177
Saraiva MJM, Melhus H, Rego K, Costa PP, Peterson PA, Goodman DS (1985b) Genetic studies on a human plasma transthyretin (prealbumin) variant associated with familial amyloidotic polyneuropathy. In: Peeters H (ed) Protides of the biological fluids, vol 33. Pergamon Press, Oxford, pp 127–130
Saraiva MJM, Alves IL, Costa PP (1989) Simplified method for screening populations at risk for transthyretin Met 30-associated familial amyloidotic polyneuropathy. Clin Chem 35:1033–1035
Sasaki H, Sakaki Y, Matsuo H, Goto I, Kuroiwa Y, Sahashi I, Takahashi A, Shinoda T, Isobe T, Takagi Y (1984) Diagnosis of familial amyloidotic polyneuropathy by recombinant DNA techniques. Biochem Biophys Res Commun 125:636–642
Sasaki H, Yoshioka N, Takagi Y, Sakaki Y (1985) Structure of the chromosomal gene for human serum prealbumin. Gene 37:191–197
Sutcliffe RG (1975) The nature and origin of the soluble protein in human amniotic fluid. Biol Rev 50:1–33
Yoshioka K, Furuya H, Sasaki H, Saraiva MJM, Costa PP, Sakaki Y (1989) Haplotype analysis of familial amyloidotic polyneuropathy. Evidence for multiple origins of the Val→Met mutation most common to the disease. Hum Genet 82:9–13
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Almeida, M.R., Alves, I.L., Sakaki, Y. et al. Prenatal diagnosis of familial amyloidotic polyneuropathy: evidence for an early expression of the associated transthyretin methionine 30. Hum Genet 85, 623–626 (1990). https://doi.org/10.1007/BF00193586
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DOI: https://doi.org/10.1007/BF00193586