Mutations in the transthyretin (TTR) gene cause familial amyloidotic polyneuropathy (FAP), an autosomal dominant peripheral neuropathy, often associated with cardiomyopathy. Liver transplant currently represents a powerful therapeutic approach for FAP patients, although its efficacy is heavily dependent both on the disease severity and on the cardiac functionality. We have investigated the TTR gene expression searching for tissue-specific additional messengers in human adult and foetal tissues as well as in eight livers from FAP transplanted patients carrying different TTR mutations (Met30, Pro36, Ala47, Arg50, and Gln89). We identified a novel transcript, recognising a different transcription start site. The additional 50-UTR sequence of this novel transcript contains regulatory boxes possibly highlighting an additional transcription start point. RNA analysis revealed that this region is represented in all foetal/adult tissues analysed. We discussed the implications of this finding which might provide perspectives for better understanding the TTR gene expression.

Transthyretin RNA profiling in livers from transplanted patients affected by familial amyloidotic polyneuropathy, and identification of a dual transcription start point.

RIMESSI, Paola;SPITALI, Pietro;CALZOLARI, Elisa;FERLINI, Alessandra
2006

Abstract

Mutations in the transthyretin (TTR) gene cause familial amyloidotic polyneuropathy (FAP), an autosomal dominant peripheral neuropathy, often associated with cardiomyopathy. Liver transplant currently represents a powerful therapeutic approach for FAP patients, although its efficacy is heavily dependent both on the disease severity and on the cardiac functionality. We have investigated the TTR gene expression searching for tissue-specific additional messengers in human adult and foetal tissues as well as in eight livers from FAP transplanted patients carrying different TTR mutations (Met30, Pro36, Ala47, Arg50, and Gln89). We identified a novel transcript, recognising a different transcription start site. The additional 50-UTR sequence of this novel transcript contains regulatory boxes possibly highlighting an additional transcription start point. RNA analysis revealed that this region is represented in all foetal/adult tissues analysed. We discussed the implications of this finding which might provide perspectives for better understanding the TTR gene expression.
Rimessi, Paola; Spitali, Pietro; Ando, Y; Mazzaferro, V; Pastorelli, F; Tassinari, Ca; Calzolari, Elisa; Salvi, F; Ferlini, Alessandra
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11392/470458
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