Long-Reads Sequencing Strategy to Localize Variants in TTN Repeated Domains.

Autor:	Perrin A; Molecular Diagnostic Laboratory, Montpellier University Hospital, Montpellier, France; PhyMedExp, University of Montpellier, INSERM, CNRS, Montpellier, France., Van Goethem C; Molecular Diagnostic Laboratory, Montpellier University Hospital, Montpellier, France., Thèze C; Molecular Diagnostic Laboratory, Montpellier University Hospital, Montpellier, France., Puechberty J; Department of Medical Genetics, Arnaud de Villeneuve Hospital, Montpellier, France., Guignard T; Laboratoire de Génétique Chromosomique, Plateforme ChromoStem, CHU de Montpellier, Université de Montpellier, Montpellier, France., Lecardonnel B; Laboratoire de Génétique Chromosomique, Plateforme ChromoStem, CHU de Montpellier, Université de Montpellier, Montpellier, France., Lacourt D; Molecular Diagnostic Laboratory, Montpellier University Hospital, Montpellier, France., Métay C; Assistance Publique-Hôpitaux de Paris (AP-HP), UF Molecular Cardiogenetics and Myogenetics, Sorbonne Université and Sorbonne Université UPMC Paris 06-Inserm UMRS974, Research Center in Myology, Pitié-Salpêtrière Hospital, Paris, France., Isapof A; Centre de Référence des Maladies Neuromusculaires Nord/Est/Ile de France, Service de Neuropédiatrie, Hôpital Trousseau, Paris, France., Whalen S; Genetics and Cytogenetics Department, Centre de Référence Déficiences Intellectuelles de Causes Rares, Pitié-Salpétrière, AP-HP, Paris, France., Ferreiro A; AP-HP, Centre de Référence des Pathologies Neuromusculaires Nord-Est-Ile de France, Institut de Myologie, GHU Pitié-Salpêtrière, Paris, France; Basic and Translational Myology Laboratory, Université de Paris BFA, UMR 8251, CNRS, Paris, France., Arne-Bes MC; Department of Neurology, Purpan University Hospital, Toulouse, France., Quijano-Roy S; AP-HP, GH Université Paris-Saclay, Neuromuscular Center, Child Neurology and ICU Department, Raymond Poincare Hospital, Garches, France; Université de Versailles, U1179 INSERM-UVSQ, Montigny, France., Nectoux J; Service de Génétique et Biologie Moléculaires, Hôpital Cochin, DMU BioPhyGen, AP-HP, Centre-Université de Paris, Paris, France., Leturcq F; Department of Genetics and Molecular Biology, AP-HP, Cochin Hospital, Paris, France., Richard P; Assistance Publique-Hôpitaux de Paris (AP-HP), UF Molecular Cardiogenetics and Myogenetics, Sorbonne Université and Sorbonne Université UPMC Paris 06-Inserm UMRS974, Research Center in Myology, Pitié-Salpêtrière Hospital, Paris, France., Larrieux M; Molecular Diagnostic Laboratory, Montpellier University Hospital, Montpellier, France., Bergougnoux A; PhyMedExp, University of Montpellier, INSERM, CNRS, Montpellier, France., Pellestor F; Laboratoire de Génétique Chromosomique, Plateforme ChromoStem, CHU de Montpellier, Université de Montpellier, Montpellier, France., Koenig M; Molecular Diagnostic Laboratory, Montpellier University Hospital, Montpellier, France; PhyMedExp, University of Montpellier, INSERM, CNRS, Montpellier, France., Cossée M; Molecular Diagnostic Laboratory, Montpellier University Hospital, Montpellier, France; PhyMedExp, University of Montpellier, INSERM, CNRS, Montpellier, France. Electronic address: mireille.cossee@inserm.fr.
Jazyk:	angličtina
Zdroj:	The Journal of molecular diagnostics : JMD [J Mol Diagn] 2022 Jul; Vol. 24 (7), pp. 719-726. Date of Electronic Publication: 2022 May 14.
DOI:	10.1016/j.jmoldx.2022.04.006
Abstrakt:	Titin protein is responsible for muscle elasticity. The TTN gene, composed of 364 exons, is subjected to extensive alternative splicing and leads to different isoforms expressed in skeletal and cardiac muscle. Variants in TTN are responsible for myopathies with a wide phenotypic spectrum and autosomal dominant or recessive transmission. The I-band coding domain, highly subject to alternative splicing, contains a three-zone block of repeated sequences with 99% homology. Sequencing and localization of variants in these areas are complex when using short-reads sequencing, a second-generation sequencing technique. We have implemented a protocol based on the third-generation sequencing technology (long-reads sequencing). This new method allows us to localize variants in these repeated areas to improve the diagnosis of TTN-related myopathies and offer the analysis of relatives in postnatal or in prenatal screening. (Copyright © 2022 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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