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Upcoming Seminars

Vincenzo Nigro, MD - "Titanic experience"

Full professor of Medical Genetics at the Department of "Precision Medicine" of the "University “Luigi Vanvitelli” of Naples, Italy and Associate Investigator of the Telethon Institute of Genetics and Medicine (TIGEM)
When Sep 17, 2019
from 12:00 PM to 01:00 PM
Where Tigem, Vesuvius Auditorium
Contact Name
Contact Phone 081-19230659
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Short CV

Abstract
Muscle sarcomeres are interconnected by titin, which serves as scaffolding filament, signaling platform, and provider of passive tension and elasticity. Titin is a huge protein encoded by the longest coding sequence produced by the human genome, composed of 364 exons. The first uses of NGS in patients with muscular disorders date back to about 10 years ago with the development of panels that included the TTN gene among the muscle genes. The experience gained already in the first analyzes was to find oneself in front of an impressive number of new titin variants of unknown significance in patients for which this gene could be a reasonable candidate, but also in normal subjects. Complex mechanisms are involved to explain how titin gene mutations may cause either hereditary cardiomyopathy or skeletal muscle diseases (or nothing). More recently, whole exome sequencing (WES) and whole genome sequencing (WGS) are increasingly used to detect small variations in muscle disorders. Although mainly truncating mutations have been identified in patients with canonical titinopathies, missense variants may similarly have a crucial role, but the signal-to-noise ratio is very low. In gnomAD 435 titin LoF and 18,600 missense variants are reported. Interpretation of TTN gene variants often requires further analysis, including a complete evaluation of the clinical phenotype (deep phenotyping), as well as messenger and protein studies. We propose a specific workflow for the clinical interpretation of titin genetic results.