Detection of TRIM32 deletions in LGMD patients analyzed by a combined strategy of CGH array and massively parallel sequencing - Université de Montpellier Accéder directement au contenu
Article Dans Une Revue European Journal of Human Genetics Année : 2015

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

Rafael de Cid
  • Fonction : Auteur
Sylvain Baulande
Jon Andoni Urtizberea
  • Fonction : Auteur
Carinne Roudaut
Audrey Criqui
  • Fonction : Auteur
Isabelle Nelson
Anna Maria Cobo
  • Fonction : Auteur
Gisèle Bonne
Jamel Chelly
  • Fonction : Auteur
  • PersonId : 899153
Isabelle Richard

Résumé

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.

Dates et versions

hal-02190709 , version 1 (22-07-2019)

Identifiants

Citer

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, 2015, 23 (7), pp.929-934. ⟨10.1038/ejhg.2014.223⟩. ⟨hal-02190709⟩
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