RAD51 haploinsufficiency causes congenital mirror movements in humans.

Christel Depienne, Delphine Bouteiller, Aurélie Méneret, Ségolène Billot, Sergiu Groppa, Stephan Klebe, Fanny Charbonnier-Beaupel, Jean-Christophe Corvol, Jean-Paul Saraiva, Norbert Brueggemann, Kailash Bhatia, Massimo Cincotta, Vanessa Brochard, Constance Flamand-Roze, Wassila Carpentier, Sabine Meunier, Yannick Marie, Marion Gaussen, Giovanni Stevanin, Rosine Wehrle, Marie Vidailhet, Christine Klein, Isabelle Dusart, Alexis Brice, Emmanuel Roze
The American Journal of Human Genetics. 2012-02-01; 90(2): 301-307
DOI: 10.1016/j.ajhg.2011.12.002


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1. Am J Hum Genet. 2012 Feb 10;90(2):301-7. doi: 10.1016/j.ajhg.2011.12.002. Epub
2012 Feb 2.

RAD51 haploinsufficiency causes congenital mirror movements in humans.

Depienne C(1), Bouteiller D, Méneret A, Billot S, Groppa S, Klebe S,
Charbonnier-Beaupel F, Corvol JC, Saraiva JP, Brueggemann N, Bhatia K, Cincotta
M, Brochard V, Flamand-Roze C, Carpentier W, Meunier S, Marie Y, Gaussen M,
Stevanin G, Wehrle R, Vidailhet M, Klein C, Dusart I, Brice A, Roze E.

Author information:
(1)INSERM, U- CRICM, Hôpital Pitié-Salpêtrière, Paris, France.

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.

Copyright © 2012 The American Society of Human Genetics. Published by Elsevier
Inc. All rights reserved.

DOI: 10.1016/j.ajhg.2011.12.002
PMCID: PMC3276668
PMID: 22305526 [Indexed for MEDLINE]

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