TY - JOUR
T1 - Congenital mirror movements
T2 - mutational analysis of RAD51 and DCC in 26 cases
AU - Méneret, Aurélie
AU - Depienne, Christel
AU - Riant, Florence
AU - Trouillard, Oriane
AU - Bouteiller, Delphine
AU - Cincotta, Massimo
AU - Bitoun, Pierre
AU - Wickert, Julia
AU - Lagroua, Isabelle
AU - Westenberger, Ana
AU - Borgheresi, Alessandra
AU - Doummar, Diane
AU - Romano, Marcello
AU - Rossi, Simone
AU - Defebvre, Luc
AU - De Meirleir, Linda
AU - Espay, Alberto J
AU - Fiori, Simona
AU - Klebe, Stephan
AU - Quélin, Chloé
AU - Rudnik-Schöneborn, Sabine
AU - Plessis, Ghislaine
AU - Dale, Russell C
AU - Sklower Brooks, Susan
AU - Dziezyc, Karolina
AU - Pollak, Pierre
AU - Golmard, Jean-Louis
AU - Vidailhet, Marie
AU - Brice, Alexis
AU - Roze, Emmanuel
N1 - © 2014 American Academy of Neurology.
PY - 2014/6/3
Y1 - 2014/6/3
N2 - 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 CMM cases. 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, 5 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.
AB - 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 CMM cases. 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, 5 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.
KW - Carrier Proteins
KW - Codon, Nonsense
KW - DNA Mutational Analysis
KW - Humans
KW - Movement Disorders
KW - Mutation
KW - Mutation, Missense
KW - Pedigree
KW - Receptors, Cell Surface
KW - Severity of Illness Index
KW - Tumor Suppressor Proteins
U2 - 10.1212/WNL.0000000000000477
DO - 10.1212/WNL.0000000000000477
M3 - Article
C2 - 24808016
VL - 82
SP - 1999
EP - 2002
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 22
ER -