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Detection of TRIM32 deletions in LGMD patients analyzed by a combined strategy of CGH array and massively parallel sequencing

Juliette Nectoux 1 Rafael de Cid 2 Sylvain Baulande 3 France Leturcq 4 Jon Andoni Urtizberea Isabelle Pénisson-Besnier 5 Aleksandra Nadaj-Pakleza 6 Carinne Roudaut 2 Audrey Criqui Lucie Orhant 1 Delphine Peyroulan 7 Raba Ben Yaou 4 Isabelle Nelson 8 Anna Maria Cobo Marie-Christine Arne-Bes 9 Emmanuelle Uro-Coste 9 Patrick Nitschke 10 Mireille Claustres 7, 11 Gisèle Bonne 8 Nicolas Lévy 12 Jamel Chelly 13 Isabelle Richard 2 Mireille Cossee 7, 11
1 Biochimie et biologie moléculaire
2 LAMBE - UMR 8587 - Laboratoire Analyse et Modélisation pour la Biologie et l'Environnement
3 Génopole [Evry]
4 Centre de recherche en myologie
5 Centre de Référence Maladies Neuromusculaires de l'Enfant et de l'Adulte, Nantes-Angers
6 Service de neurologie [Angers]
7 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
8 Centre de recherche en myologie
9 CHU Toulouse [Toulouse]
10 BIP-D - Plate Forme Paris Descartes de Bioinformatique
11 LGMR - Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques
12 GMGF - Génétique Médicale et Génomique Fonctionnelle
13 UMR_S567 / UMR 8104 - Institut Cochin
Abstract : Defects in TRIM32 were reported in limb-girdle muscular dystrophy type 2H (LGMD2H), sarcotubular myopathies (STM) and in Bardet-Biedl syndrome. Few cases have been described to date in LGMD2H/STM, but this gene is not systematically analysed because of the absence of specific signs and difficulties in protein analysis. By using high-throughput variants screening techniques, we identified variants in TRIM32 in two patients presenting nonspecific LGMD. We report the first case of total inactivation by homozygous deletion of the entire TRIM32 gene. Of interest, the deletion removes part of the ASTN2 gene, a large gene in which TRIM32 is nested. Despite the total TRIM32 gene inactivation, the patient does not present a more severe phenotype. However, he developed a mild progressive cognitive impairment that may be related to the loss of function of ASTN2 because association between ASTN2 heterozygous deletions and neurobehavioral disorders was previously reported. Regarding genomic characteristics at breakpoint of the deleted regions of TRIM32, we found a high density of repeated elements, suggesting a possible hotspot. These observations illustrate the importance of high-throughput technologies for identifying molecular defects in LGMD, confirm that total loss of function of TRIM32 is not associated with a specific phenotype and that TRIM32/ASTN2 inactivation could be associated with cognitive impairment.
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https://hal.umontpellier.fr/hal-02190709
Contributeur : Cécile Nowak <>
Soumis le : lundi 22 juillet 2019 - 16:48:22
Dernière modification le : vendredi 27 mars 2020 - 02:46:59

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UNIV-MONTPELLIER | UNAM | UNIV-CERGY | CNRS | CEA | U974 | CEA-UPSAY | LAMBE | INC-CNRS | UPMC | UNIV-PARIS5 | BS | UNIV-AMU | MMG | SORBONNE-UNIVERSITE | UNIV-EVRY | SU-MEDECINE | UNIV-ANGERS | USPC | UNIV-PARIS-SACLAY

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Juliette Nectoux, Rafael de Cid, Sylvain Baulande, France Leturcq, Jon Andoni Urtizberea, et al.. Detection of TRIM32 deletions in LGMD patients analyzed by a combined strategy of CGH array and massively parallel sequencing. European Journal of Human Genetics, Nature Publishing Group, 2015, 23 (7), pp.929-934. ⟨10.1038/ejhg.2014.223⟩. ⟨hal-02190709⟩

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