A novel DCC mutation and genetic heterogeneity in congenital mirror movements.
OBJECTIVE
DCC is the receptor for netrin, a protein that guides axon migration of developing neurons across the body's midline. Mutations in the DCC gene were recently identified in 2 families with congenital mirror movements (MM). The objective was to study clinical and genetic characteristics of 3 European families with MM and to test whether this disorder is genetically homogeneous.


METHODS
We studied 3 MM families with a total of 13 affected subjects. Each patient had a standardized interview and neurologic examination, focusing on the phenomenology and course of the MM. The severity of MM was also assessed. Molecular analysis of DCC was performed in the index cases. In addition, linkage analysis of the DCC locus was performed in a large French family.


RESULTS
The clinical expression and course of MM were very similar in all the affected subjects, regardless of DCC mutational status. However, slight intersubject variability in the severity of MM was noted within each family. Onset always occurred in infancy or early childhood, and MM did not deteriorate over time. Motor disability due to MM was mild and restricted to activities that require independent movements of the 2 hands. We found a novel mutation in the DCC gene in an Italian family with MM associated with abnormal ipsilateral corticospinal projection. The DCC locus was excluded in the French family.


CONCLUSIONS
DCC has a crucial role in the development of corticospinal tracts in humans. Congenital MM is genetically heterogeneous, despite its clinical homogeneity.
INSERM, UMRS 975, and CNRS 7225-CRICM, Pitié-Salpêtrière Hospital, Paris, France.
C
C
Depienne
M
M
Cincotta
S
S
Billot
D
D
Bouteiller
S
S
Groppa
V
V
Brochard
C
C
Flamand
C
C
Hubsch
S
S
Meunier
F
F
Giovannelli
S
S
Klebe
J C
JC
Corvol
M
M
Vidailhet
A
A
Brice
E
E
Roze
D000328:Adult; D017668:Age of Onset; D000368:Aged; D020820:Dyskinesias / Q000235:genetics; D005260:Female; D005602:France; D016163:Genes, DCC / Q000235:genetics*; D018740:Genetic Heterogeneity; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010146:Pain / Q000209:etiology; D010375:Pedigree; D010641:Phenotype; D012720:Severity of Illness Index; D019956:Stereotypic Movement Disorder / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D034941:Upper Extremity / Q000503:physiopathology