Detection of three transthyretin gene mutations in familial amyloidotic polyneuropathy by analysis of DNA extracted from formalin-fixed and paraffin-embedded tissues

We identified three different missense mutations of the transthyretin (TTR) gene in three Japanese patients with familial amyloidotic polyneuropathy by analysis of their DNAs extracted from formalin-fixed and paraffin-embedded tissues. Patient 1 carried the TTR methionine-30 (Met) mutation (G to A transition at position 1679). DNA sequencing analysis of the TTR gene from patient 2 showed a G to T transversion at position 3830 in exon 3, resulting in an amino acid replacement of serine-50 (Ser) with isoleucine (Ile). Patient 3 had the novel mutation (G to T transversion at position 7314) in exon 4, resulting in an amino acid replacement of alanine-109 (Ala) with Ser. We established DNA diagnostic methods for detecting TTR Ile(50) by polymerase chain reaction (PCR)-induced mutation restriction analysis and for TTR Ser(109) by PCR-restriction fragment length polymorphism. Gene analysis of archival paraffin-embedded tissues is useful for the precise diagnosis of FAP and for clarifying its molecular pathogenesis in patients for whom fresh genomic DNA is not available. (C) 1997 Elsevier Science B.V.