Prenatal diagnosis of familial amyloidotic polyneuropathy: evidence for an early expression of the associated transthyretin methionine 30

• Published in: Human genetics Vol. 85; no. 6; p. 623
• Main Authors: Almeida, M R, Alves, I L, Sakaki, Y, Costa, P P, Saraiva, M J
• Format: Journal Article
• Language: English
• Published: Germany 01.10.1990
• Subjects: Amniotic Fluid - chemistry; Amyloid - biosynthesis; Amyloidosis - diagnosis; Female; Gene Expression; Humans; Nucleic Acid Hybridization; Oligonucleotide Probes; Peripheral Nervous System Diseases - diagnosis; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Prealbumin - biosynthesis; Pregnancy; Prenatal Diagnosis
• ISSN: 0340-6717
• DOI: 10.1007/BF00193586

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.