Congenital mirror movements: Mutational analysis of RAD51 and DCC in 26 cases

Aurélie Méneret, Christel Depienne, Florence Riant, Oriane Trouillard, Delphine Bouteiller, Massimo Cincotta, Pierre Bitoun, Julia Wickert, Isabelle Lagroua, Ana Westenberger, Alessandra Borgheresi, Diane Doummar, Marcello Romano, Simone Rossi, Luc Defebvre, Linda De Meirleir, Alberto J. Espay, Simona Fiori, Stephan Klebe, Chloé QuélinSabine Rudnik-Schöneborn, Ghislaine Plessis, Russell C. Dale, Susan Sklower Brooks, Karolina Dziezyc, Pierre Pollak, Jean Louis Golmard, Marie Vidailhet, Alexis Brice, Emmanuel Roze

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: We screened a large series of individuals with congenital mirror movements (CMM) for mutations in the 2 identified causative genes, DCC and RAD51. Methods: We studied 6 familial and 20 simplex CMMcases. Each patient had a standardized neurologic assessment. Analysis of DCC and RAD51 coding regions included Sanger sequencing and a quantitative method allowing detection of micro rearrangements. We then compared the frequency of rare variants predicted to be pathogenic by either the PolyPhen-2 or the SIFT algorithm in our population and in the 4,300 controls of European origin on the Exome Variant Server. Results: We found 3 novel truncating mutations of DCC that segregate with CMM in 4 of the 6 families. Among the 20 simplex cases, we found one exonic deletion of DCC, one DCC mutation leading to a frameshift, = missense variants in DCC, and 2 missense variants in RAD51. All 7 missense variants were predicted to be pathogenic by one or both algorithms. Statistical analysis showed that the frequency of variants predicted to be deleterious was significantly different between patients and controls (p <0.001 for both RAD51 and DCC). Conclusion: Mutations and variants in DCC and RAD51 are strongly associated with CMM, but additional genes causing CMM remain to be discovered.

Original languageEnglish
Pages (from-to)1999-2002
Number of pages4
JournalNeurology
Volume82
Issue number22
DOIs
Publication statusPublished - Jun 3 2014

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

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