title: Transthyretin RNA profiling in livers from transplanted patients affected by familial amyloidotic polyneuropathy, and identification of a dual transcription start point.
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 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.
authors.affiliation: Dipartimento di Medicina Sperimentale e Diagnostica, Sezione di Genetica Medica, University of Ferrara, Ferrara, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Rimessi
authors.forename: Pietro
authors.initials: P
authors.lastname: Spitali
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ando
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mazzaferro
authors.forename: Francesca
authors.initials: F
authors.lastname: Pastorelli
authors.forename: Carlo Alberto
authors.initials: CA
authors.lastname: Tassinari
authors.forename: Elisa
authors.initials: E
authors.lastname: Calzolari
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Salvi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferlini
mesh_terms: D028227:Amyloid Neuropathies, Familial / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D000818:Animals; D001483:Base Sequence; D005260:Female; D005333:Fetus / Q000737:chemistry; D020869:Gene Expression Profiling / Q000379:methods*; D005819:Genetic Markers; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D011228:Prealbumin / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D013045:Species Specificity; D014158:Transcription, Genetic
chemical_list: D005819:Genetic Markers; D011228:Prealbumin; D012333:RNA, Messenger