| Popis: |
We identified three novel variants of transthyretin (TTR), TTR-Cys 114, TTR-Gly 42, and TTR-Arg 50, in three Japanese kindreds with familial amyloidotic polyneuropathy. Amyloid deposits reacted with anti-TTR serum. Amino acid mutations were deduced from TTR gene sequences determined. Every four exons were amplified by PCR, cloned into M13 vectors and randomly sequenced by Sanger’s method. Base change detected was confirmed by restriction site analysis and ASO differential hybridization analysis. Two genetically different kindreds may originate in rather small area, one was our kindred associated with TTR-Cys 114 in Kunimi and other was already reported FAP type I with TTR-Met 30 in Arao. No cases of FAP as identified by us have been reported outside of Japan and the possibility that the gene mutations occurred originally within Japan can not be excluded. Our discovery of the three new variants adds to the substantial evidence supporting that TTR related FAP are far more varied and prevalent than previously thought. |
