TY - JOUR
T1 - Transthyretin RNA profiling in livers from transplanted patients affected by familial amyloidotic polyneuropathy, and identification of a dual transcription start point
AU - Rimessi, Paola
AU - Spitali, Pietro
AU - Ando, Yukio
AU - Mazzaferro, Vincenzo
AU - Pastorelli, Francesca
AU - Tassinari, Carlo Alberto
AU - Calzolari, Elisa
AU - Salvi, Fabrizio
AU - Ferlini, Alessandra
PY - 2006/3
Y1 - 2006/3
N2 - 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 5′-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.
AB - 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 5′-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.
KW - Familial amyloidotic polyneuropathy
KW - Liver
KW - Mutations
KW - RNA
KW - Transcription
KW - Transthyretin
UR - http://www.scopus.com/inward/record.url?scp=33645960125&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33645960125&partnerID=8YFLogxK
U2 - 10.1111/j.1478-3231.2005.01208.x
DO - 10.1111/j.1478-3231.2005.01208.x
M3 - Article
C2 - 16448460
AN - SCOPUS:33645960125
VL - 26
SP - 211
EP - 220
JO - Liver International
JF - Liver International
SN - 1478-3223
IS - 2
ER -