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Article Dans Une Revue American Journal of Human Genetics Année : 2012

RAD51 haploinsufficiency causes congenital mirror movements in humans

Christel Depienne
Delphine Bouteiller
  • Fonction : Auteur
Aurélie Méneret
  • Fonction : Auteur
Ségolène Billot
  • Fonction : Auteur
Sergiu Groppa
  • Fonction : Auteur
Stephan Klebe
  • Fonction : Auteur
Fanny Charbonnier-Beaupel
  • Fonction : Auteur
Jean-Christophe Corvol
Jean-Paul Saraiva
  • Fonction : Auteur
Norbert Brueggemann
  • Fonction : Auteur
Kailash Bhatia
  • Fonction : Auteur
Massimo Cincotta
  • Fonction : Auteur
Vanessa Brochard
  • Fonction : Auteur
Constance Flamand-Roze
  • Fonction : Auteur
Sabine Meunier
  • Fonction : Auteur
Yannick Marie
  • Fonction : Auteur
  • PersonId : 760117
  • IdRef : 186339437
Marion Gaussen
  • Fonction : Auteur
Giovanni Stevanin
Rosine Wehrle
  • Fonction : Auteur
Marie Vidailhet
Christine Klein
  • Fonction : Auteur
Alexis Brice
  • Fonction : Auteur
Emmanuel Roze

Résumé

Congenital mirror movements (CMM) are characterized by involuntary movements of one side of the body that mirror intentional movements on the opposite side. CMM reflect dysfunctions and structural abnormalities of the motor network and are mainly inherited in an autosomal-dominant fashion. Recently, heterozygous mutations in DCC, the gene encoding the receptor for netrin 1 and involved in the guidance of developing axons toward the midline, have been identified but CMM are genetically heterogeneous. By combining genome-wide linkage analysis and exome sequencing, we identified heterozygous mutations introducing premature termination codons in RAD51 in two families with CMM. RAD51 mRNA was significantly downregulated in individuals with CMM resulting from the degradation of the mutated mRNA by nonsense-mediated decay. RAD51 was specifically present in the developing mouse cortex and, more particularly, in a subpopulation of corticospinal axons at the pyramidal decussation. The identification of mutations in RAD51, known for its key role in the repair of DNA double-strand breaks through homologous recombination, in individuals with CMM reveals a totally unexpected role of RAD51 in neurodevelopment. These findings open a new field of investigation for researchers attempting to unravel the molecular pathways underlying bimanual motor control in humans.

Dates et versions

hal-01543631 , version 1 (21-06-2017)

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Citer

Christel Depienne, Delphine Bouteiller, Aurélie Méneret, Ségolène Billot, Sergiu Groppa, et al.. RAD51 haploinsufficiency causes congenital mirror movements in humans. American Journal of Human Genetics, 2012, 90 (2), pp.301--307. ⟨10.1016/j.ajhg.2011.12.002⟩. ⟨hal-01543631⟩
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