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.

Iorio, A., De Lillo, A., De Angelis, F., Di Girolamo, M., Luigetti, M., Sabatelli, M., et al. (2017). Non-coding variants contribute to the clinical heterogeneity of TTR amyloidosis. EUROPEAN JOURNAL OF HUMAN GENETICS, 25(9), 1055-1060 [10.1038/ejhg.2017.95].

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

Iorio, Andrea;De Lillo, Antonella;De Angelis, Flavio;Fuciarelli, Maria;Polimanti, Renato
2017

Abstract

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.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/08
English
Con Impact Factor ISI
Amyloidosis; Female; Genotype; Heterozygote; Humans; Male; Prealbumin; Mutation; Phenotype; Genetics; Genetics (clinical)
http://www.nature.com/ejhg/index.html
Iorio, A., De Lillo, A., De Angelis, F., Di Girolamo, M., Luigetti, M., Sabatelli, M., et al. (2017). Non-coding variants contribute to the clinical heterogeneity of TTR amyloidosis. EUROPEAN JOURNAL OF HUMAN GENETICS, 25(9), 1055-1060 [10.1038/ejhg.2017.95].
Iorio, A; De Lillo, A; De Angelis, F; Di Girolamo, M; Luigetti, M; Sabatelli, M; Pradotto, L; Mauro, A; Mazzeo, A; Stancanelli, C; Perfetto, F; Frusconi, S; My, F; Manfellotto, D; Fuciarelli, M; Polimanti, R
Articolo su rivista
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/192983
Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 15
  • ???jsp.display-item.citation.isi??? 13
social impact