Non-coding variants contribute to the clinical heterogeneity of TTR amyloidosis

Mario Sabatelli, Marco Luigetti, Andrea Iorio, Antonella De Lillo, Flavio De Angelis, Marco Di Girolamo, Luca Pradotto, Alessandro Mauro, Anna Mazzeo, Claudia Stancanelli, Federico Perfetto, Sabrina Frusconi, Filomena My, Dario Manfellotto, Maria Fuciarelli, Renato Polimanti

Risultato della ricerca: Contributo in rivistaArticolo in rivista

9 Citazioni (Scopus)


Coding mutations in TTR gene cause a rare hereditary form of systemic amyloidosis, which has a complex genotype-phenotype correlation. We investigated the role of non-coding variants in regulating TTR gene expression and consequently amyloidosis symptoms. We evaluated the genotype-phenotype correlation considering the clinical information of 129 Italian patients with TTR amyloidosis. Then, we conducted a re-sequencing of TTR gene to investigate how non-coding variants affect TTR expression and, consequently, phenotypic presentation in carriers of amyloidogenic mutations. Polygenic scores for genetically determined TTR expression were constructed using data from our re-sequencing analysis and the GTEx (Genotype-Tissue Expression) project. We confirmed a strong phenotypic heterogeneity across coding mutations causing TTR amyloidosis. Considering the effects of non-coding variants on TTR expression, we identified three patient clusters with specific expression patterns associated with certain phenotypic presentations, including late onset, autonomic neurological involvement, and gastrointestinal symptoms. This study provides novel data regarding the role of non-coding variation and the gene expression profiles in patients affected by TTR amyloidosis, also putting forth an approach that could be used to investigate the mechanisms at the basis of the genotype-phenotype correlation of the disease.
Lingua originaleEnglish
pagine (da-a)1055-1060
Numero di pagine6
RivistaEuropean Journal of Human Genetics
Stato di pubblicazionePubblicato - 2017


  • Amyloidosis
  • Female
  • Genetics
  • Genetics (clinical)
  • Genotype
  • Heterozygote
  • Humans
  • Male
  • Mutation
  • Phenotype
  • Prealbumin


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