Effectiveness and Impact of Transcript Analysis in Clinical Genetics Daily Practice
Broad-spectrum genetic tests often lead to the identification of variants of uncertain significance (VUS), a major issue in modern clinical genetics. A fair proportion of VUS may alter the splicing processes, but their interpretation is challenging. This study aimed at providing a classification approach for VUS potentially-affecting splicing by integrating transcript analysis from peripheral blood mRNA into routine diagnostics. VUS in DICER1, MSH2, MLH1, DYNC1H1, RPS6KA3, and SCN9A, found in patients with phenotypes compatible with the related syndromes, altered splicing, leading to their re-classification as Pathogenic/Likely Pathogenic. This had a significant clinical impact for different diseases, from hereditary tumor predisposition to neurological and congenital syndromic disorders. Transcript analysis is valuable in VUS clinical evaluation, and its incorporation into routine diagnostic workflows facilitates timely and accurate clinical decision-making.
Authors
- Emanuele Panza (ORCID: https://orcid.org/0000-0002-2338-1139)
- Giovanni Innella (ORCID: https://orcid.org/0000-0002-6909-2412)
- Carlotta Pia Cristalli (ORCID: https://orcid.org/0000-0003-1428-8714)
- Eliana Zacchi
- Daniela Turchetti (ORCID: https://orcid.org/0000-0002-6792-3921)
- Alessandro Vaisfeld (ORCID: https://orcid.org/0000-0001-8413-621X)
- Sara Taormina
- Emanuele Coccia (ORCID: https://orcid.org/0000-0003-3389-0989)
- Chiara Diquigiovanni (ORCID: https://orcid.org/0000-0003-3124-6946)
- Giulia Lanzoni (ORCID: https://orcid.org/0009-0008-8220-3229)
- Flavia Palombo (ORCID: https://orcid.org/0000-0002-1639-3764)
- Cesare Rossi (ORCID: https://orcid.org/0000-0003-1826-615X)
- Elena Bonora (ORCID: https://orcid.org/0000-0001-6132-7734)
- Valério Carelli (ORCID: https://orcid.org/0000-0003-4923-6404)
- Cecilia Evangelisti (ORCID: https://orcid.org/0000-0002-0877-7696)
- Isabelle Bacchi (ORCID: https://orcid.org/0009-0007-3981-5994)
- Simona Ferrari
- Stefania Calabrese
Institutions
- Azienda USL di Bologna (IT)
- Istituto delle Scienze Neurologiche di Bologna (IT)
- University of Bologna (IT)
Publication Details
- Journal
- Clinical Genetics
- Published
- 2024-12-21
- DOI
- https://doi.org/10.1111/cge.14684
- Citations
- 1
- Primary Topic
- RNA modifications and cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.23