Novel dominant distal titinopathy phenotype associated with copy number variation
Abstract 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...
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2021-09-01
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Series: | Annals of Clinical and Translational Neurology |
Online Access: | https://doi.org/10.1002/acn3.51434 |
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doaj-82ea21e674cb43eba36e02589a86a40a2021-09-06T06:03:43ZengWileyAnnals of Clinical and Translational Neurology2328-95032021-09-01891906191210.1002/acn3.51434Novel dominant distal titinopathy phenotype associated with copy number variationAurélien Perrin0Raul Juntas Morales1Françoise Chapon2Corinne Thèze3Delphine Lacourt4Henri Pégeot5Emmanuelle Uro‐Coste6Diane Giovannini7Nicolas Leboucq8Martial Mallaret9Emmeline Lagrange10Valérie Rigau11Karen Gaudon12Pascale Richard13Michel Koenig14Corinne Métay15Mireille Cossée16Laboratoire de Génétique Moléculaire Centre Hospitalier Universitaire de Montpellier Montpellier FranceLaboratoire de Génétique Moléculaire Centre Hospitalier Universitaire de Montpellier Montpellier FranceDépartement de pathologie Centre de Compétence des Maladies Neuromusculaires Centre Hospitalier Universitaire de Caen Caen FranceLaboratoire de Génétique Moléculaire Centre Hospitalier Universitaire de Montpellier Montpellier FranceLaboratoire de Génétique Moléculaire Centre Hospitalier Universitaire de Montpellier Montpellier FranceLaboratoire de Génétique Moléculaire Centre Hospitalier Universitaire de Montpellier Montpellier FranceDépartement d’Anatomie et Cytologie Pathologiques Centre Hospitalier Universitaire Toulouse Toulouse FranceService d’Anatomie et de Cytologie Pathologiques CHU Grenoble‐Alpes Grenoble FranceService de Neuroradiologie Centre Hospitalier Universitaire de Montpellier Montpellier 34090 FranceCentre de Compétences des Maladies Neuro Musculaires Centre Hospitalier Universitaire Grenoble Alpes Grenoble FranceCentre de Compétences des Maladies Neuro Musculaires Centre Hospitalier Universitaire Grenoble Alpes Grenoble FranceDépartement de Pathologie Centre Hospitalier Universitaire Montpellier Montpellier FranceUnité Fonctionnelle de Cardiogénétique et Myogénétique moleculaire et cellulaire Centre de Génétique Moléculaire et Chromosomique et INSERM UMRS 974 Institut de Myologie Groupe Hospitalier La Pitié‐Salpêtrière‐Charles Foix Paris INSERM UMRS1166 UPMC Paris 6 Paris FranceUnité Fonctionnelle de Cardiogénétique et Myogénétique moleculaire et cellulaire Centre de Génétique Moléculaire et Chromosomique et INSERM UMRS 974 Institut de Myologie Groupe Hospitalier La Pitié‐Salpêtrière‐Charles Foix Paris INSERM UMRS1166 UPMC Paris 6 Paris FranceLaboratoire de Génétique Moléculaire Centre Hospitalier Universitaire de Montpellier Montpellier FranceUnité Fonctionnelle de Cardiogénétique et Myogénétique moleculaire et cellulaire Centre de Génétique Moléculaire et Chromosomique et INSERM UMRS 974 Institut de Myologie Groupe Hospitalier La Pitié‐Salpêtrière‐Charles Foix Paris INSERM UMRS1166 UPMC Paris 6 Paris FranceLaboratoire de Génétique Moléculaire Centre Hospitalier Universitaire de Montpellier Montpellier FranceAbstract 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.https://doi.org/10.1002/acn3.51434 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Aurélien Perrin Raul Juntas Morales Françoise Chapon Corinne Thèze Delphine Lacourt Henri Pégeot Emmanuelle Uro‐Coste Diane Giovannini Nicolas Leboucq Martial Mallaret Emmeline Lagrange Valérie Rigau Karen Gaudon Pascale Richard Michel Koenig Corinne Métay Mireille Cossée |
spellingShingle |
Aurélien Perrin Raul Juntas Morales Françoise Chapon Corinne Thèze Delphine Lacourt Henri Pégeot Emmanuelle Uro‐Coste Diane Giovannini Nicolas Leboucq Martial Mallaret Emmeline Lagrange Valérie Rigau Karen Gaudon Pascale Richard Michel Koenig Corinne Métay Mireille Cossée Novel dominant distal titinopathy phenotype associated with copy number variation Annals of Clinical and Translational Neurology |
author_facet |
Aurélien Perrin Raul Juntas Morales Françoise Chapon Corinne Thèze Delphine Lacourt Henri Pégeot Emmanuelle Uro‐Coste Diane Giovannini Nicolas Leboucq Martial Mallaret Emmeline Lagrange Valérie Rigau Karen Gaudon Pascale Richard Michel Koenig Corinne Métay Mireille Cossée |
author_sort |
Aurélien Perrin |
title |
Novel dominant distal titinopathy phenotype associated with copy number variation |
title_short |
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_sort |
novel dominant distal titinopathy phenotype associated with copy number variation |
publisher |
Wiley |
series |
Annals of Clinical and Translational Neurology |
issn |
2328-9503 |
publishDate |
2021-09-01 |
description |
Abstract 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. |
url |
https://doi.org/10.1002/acn3.51434 |
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