Most recent common ancestor of TTR Val30Met mutation in Italian population and its potential role in genotype-phenotype correlation. (June 2015)

• Record Type: Journal Article
• Authors: Iorio, Andrea; De Angelis, Flavio; Di Girolamo, Marco; Luigetti, Marco; Pradotto, Luca; Mauro, Alessandro; Manfellotto, Dario; Fuciarelli, Maria; Polimanti, Renato
• Is Part Of: Amyloid. Volume 22:Number 2(2015:Jun.)
• Page Start: 73
• Page End: 78
• Publication Date: 2015-06
• Subjects: Amyloidosis -- Periodicals; 616.3995
• DOI: 10.3109/13506129.2014.994597
• Languages: English
• ISSNs: 1350-6129

Abstract

<abstract> <title>Abstract</title> <p> <italic>Introduction</italic>: Transthyretin (TTR)-related amyloidosis is characterized by autosomal transmission of amyloidogenic mutated <italic>TTR</italic>. Val30Met is one of the most common amyloidogenic <italic>TTR</italic> 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.</p> <p> <italic>Methods</italic>: We analyzed the origin of Italian Val30Met through 11 microsatellite markers around the <italic>TTR</italic> gene in 29 patients and 34 healthy controls.</p> <p> <italic>Results</italic>: Our 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.</p> <p> <italic>Discussion and conclusions</italic>: Italian 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 <italic>TTR</italic> non-coding regions may contribute to phenotypic heterogeneity.</p> </abstract>