Most recent common ancestor of TTR Val30Met mutation in Italian population and its potential role in genotype-phenotype correlation

Andrea Iorio, Flavio De Angelis, Marco Di Girolamo, Marco Luigetti, Luca Pradotto, Alessandro Mauro, Dario Manfellotto, Maria Fuciarelli, Renato Polimanti*

*Autore corrispondente per questo lavoro

Risultato della ricerca: Contributo in rivistaArticolo

13 Citazioni (Scopus)

Abstract

INTRODUCTION:\r\nTransthyretin (TTR)-related amyloidosis is characterized by autosomal transmission of amyloidogenic mutated TTR. Val30Met is one of the most common amyloidogenic TTR mutations, showing a worldwide distribution with phenotypic heterogeneity among human populations. Multiple founder mutations for Val30Met foci have been hypothesized and the different origins may explain the phenotypic variability. The aim of our study is to determine the origin of Italian Val30Met and to analyze the genetic relationship of other Val30Met foci.\r\nMETHODS:\r\nWe analyzed the origin of Italian Val30Met through 11 microsatellite markers around the TTR gene in 29 patients and 34 healthy controls.\r\nRESULTS:\r\nOur genetic analysis showed an estimated age of origin of 34-36 generations ago for the Italian Val30Met. Comparing Italian Val30Met haplotypes with those from Sweden and Portugal highlights relevant differences that seem to be consistent with an independent origin of Italian Val30Met mutation. This genetic evidence agrees with the disease phenotypic variation in these populations.\r\nDISCUSSION AND CONCLUSIONS:\r\nItalian Val30Met mutation should have originated before the Portuguese and Swedish Val30Met ones (which arose through independent mutational events). This indicates a genetic diversity in the surrounding regions of three different Val30Met mutations, supporting the hypothesis that TTR non-coding regions may contribute to phenotypic heterogeneity.
Lingua originaleInglese
pagine (da-a)73-78
Numero di pagine6
RivistaAMYLOID
Volume22
Numero di pubblicazione2
DOI
Stato di pubblicazionePubblicato - 2015

All Science Journal Classification (ASJC) codes

  • Medicina Interna

Keywords

  • Founder mutation
  • phenotypic heterogeneity
  • rare disease
  • short tandem repeat
  • transthyretin-related amyloidosis

Fingerprint

Entra nei temi di ricerca di 'Most recent common ancestor of TTR Val30Met mutation in Italian population and its potential role in genotype-phenotype correlation'. Insieme formano una fingerprint unica.

Cita questo