[Diagnosis by recombinant DNA techniques and clinical features of familial amyloid polyneuropathy]

Serum prealbumin variant with a substitution of methionine (Met) for valine (Val) at position 30 is known to be related to Andrade type familial amyloid polyneuropathy (FAP). Recently, the diagnosis of FAP by recombinant DNA techniques has been established. The DNA diagnosis is based on the fact that a nucleotide substitution responsible for Val-Met change results in formation of new restriction sites for Nsi 1 and Bal 1. We conducted the DNA diagnosis studies of 30 constituents of FAP pedigrees originated from Nagano and Hiroshima Prefectures, and compared the results with clinical features. Clinical features of the patients originated from Ogawa Village area in Nagano Prefecture and from Hiroshima Prefecture showed Andrade type FAP such as polyneuropathy and autonomic nervous disorders. Those of the patients from Iiyama City in Nagano Prefecture showed central nervous involvement such as cerebellar ataxia and/or pyramidal tract signs in addition to the clinical features of Andrade type FAP (Iiyama type). DNA prepared from white blood cells was digested with restriction endonuclease Nsi 1 or Bal 1 and subjected to Southern blot hybridization. The resulting DNA segments were fractionated by agarose gel electrophoresis. The gel was alkalized to convert the double-strand DNA to a single-strand form, which then was absorbed on a nylon membrane filter. The prealbumin cDNA was labelled with 32P as a probe. The probe was hybridized with DNA segments on a filter. The filter was placed on the X-ray film to obtain the autoradiogram.(ABSTRACT TRUNCATED AT 250 WORDS)