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Novel dominant distal titinopathy phenotype associated with copy number variation

The aim of this study was to analyze patients from two distinct families with a novel distal titinopathy phenotype associated with exactly the same CNV in the TTN gene. We used an integrated strategy combining deep phenotyping and complete molecular analyses in patients. The CNV is the most proximal...

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Autores principales: Perrin, Aurélien, Juntas Morales, Raul, Chapon, Françoise, Thèze, Corinne, Lacourt, Delphine, Pégeot, Henri, Uro‐Coste, Emmanuelle, Giovannini, Diane, Leboucq, Nicolas, Mallaret, Martial, Lagrange, Emmeline, Rigau, Valérie, Gaudon, Karen, Richard, Pascale, Koenig, Michel, Métay, Corinne, Cossée, Mireille
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419403/
https://www.ncbi.nlm.nih.gov/pubmed/34312993
http://dx.doi.org/10.1002/acn3.51434
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author Perrin, Aurélien
Juntas Morales, Raul
Chapon, Françoise
Thèze, Corinne
Lacourt, Delphine
Pégeot, Henri
Uro‐Coste, Emmanuelle
Giovannini, Diane
Leboucq, Nicolas
Mallaret, Martial
Lagrange, Emmeline
Rigau, Valérie
Gaudon, Karen
Richard, Pascale
Koenig, Michel
Métay, Corinne
Cossée, Mireille
author_facet Perrin, Aurélien
Juntas Morales, Raul
Chapon, Françoise
Thèze, Corinne
Lacourt, Delphine
Pégeot, Henri
Uro‐Coste, Emmanuelle
Giovannini, Diane
Leboucq, Nicolas
Mallaret, Martial
Lagrange, Emmeline
Rigau, Valérie
Gaudon, Karen
Richard, Pascale
Koenig, Michel
Métay, Corinne
Cossée, Mireille
author_sort Perrin, Aurélien
collection PubMed
description The aim of this study was to analyze patients from two distinct families with a novel distal titinopathy phenotype associated with exactly the same CNV in the TTN gene. We used an integrated strategy combining deep phenotyping and complete molecular analyses in patients. The CNV is the most proximal out‐of‐frame TTN variant reported and leads to aberrant splicing transcripts leading to a frameshift. In this case, the dominant effect would be due to dominant‐negative and/or haploinsufficiency. Few CNV in TTN have been reported to date. Our data represent a novel phenotype–genotype association and provides hypotheses for its dominant effects.
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spelling pubmed-84194032021-09-08 Novel dominant distal titinopathy phenotype associated with copy number variation Perrin, Aurélien Juntas Morales, Raul Chapon, Françoise Thèze, Corinne Lacourt, Delphine Pégeot, Henri Uro‐Coste, Emmanuelle Giovannini, Diane Leboucq, Nicolas Mallaret, Martial Lagrange, Emmeline Rigau, Valérie Gaudon, Karen Richard, Pascale Koenig, Michel Métay, Corinne Cossée, Mireille Ann Clin Transl Neurol Brief Communication The aim of this study was to analyze patients from two distinct families with a novel distal titinopathy phenotype associated with exactly the same CNV in the TTN gene. We used an integrated strategy combining deep phenotyping and complete molecular analyses in patients. The CNV is the most proximal out‐of‐frame TTN variant reported and leads to aberrant splicing transcripts leading to a frameshift. In this case, the dominant effect would be due to dominant‐negative and/or haploinsufficiency. Few CNV in TTN have been reported to date. Our data represent a novel phenotype–genotype association and provides hypotheses for its dominant effects. John Wiley and Sons Inc. 2021-07-27 /pmc/articles/PMC8419403/ /pubmed/34312993 http://dx.doi.org/10.1002/acn3.51434 Text en © 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Brief Communication
Perrin, Aurélien
Juntas Morales, Raul
Chapon, Françoise
Thèze, Corinne
Lacourt, Delphine
Pégeot, Henri
Uro‐Coste, Emmanuelle
Giovannini, Diane
Leboucq, Nicolas
Mallaret, Martial
Lagrange, Emmeline
Rigau, Valérie
Gaudon, Karen
Richard, Pascale
Koenig, Michel
Métay, Corinne
Cossée, Mireille
Novel dominant distal titinopathy phenotype associated with copy number variation
title Novel dominant distal titinopathy phenotype associated with copy number variation
title_full Novel dominant distal titinopathy phenotype associated with copy number variation
title_fullStr Novel dominant distal titinopathy phenotype associated with copy number variation
title_full_unstemmed Novel dominant distal titinopathy phenotype associated with copy number variation
title_short Novel dominant distal titinopathy phenotype associated with copy number variation
title_sort novel dominant distal titinopathy phenotype associated with copy number variation
topic Brief Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419403/
https://www.ncbi.nlm.nih.gov/pubmed/34312993
http://dx.doi.org/10.1002/acn3.51434
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