Congenital Mirror Movements Due to RAD51: Cosegregation with a Nonsense Mutation in a Norwegian Pedigree and Review of the Literature.
BACKGROUND
Autosomal dominant congenital mirror movements (CMM) is a neurodevelopmental disorder characterized by early onset involuntary movements of one side of the body that mirror intentional movements on the contralateral side; these persist throughout life in the absence of other neurological symptoms. The main culprit genes responsible for this condition areRAD51andDCC. This condition has only been reported in a few families, and the molecular mechanisms linkingRAD51mutations and mirror movements (MM) are poorly understood.


METHODS
We collected demographic, clinical, and genetic data of a new family with CMM due to a truncating mutation ofRAD51.We reviewed the literature to identify all reported patients with CMM due toRAD51mutations.


RESULTS
We identified a heterozygous nonsense mutation c.760C>T (p.Arg254*) in eight subjects: four with obvious and disabling MM, and four with a mild phenotype. Including our new family, we identified 32 patients from 6 families with CMM linked toRAD51variants.


CONCLUSIONS
Our findings further support the involvement ofRAD51in CMM pathogenesis. Possible molecular mechanisms involved in CMM pathogenesis are discussed.
Sorbonne Universités, UPMC Univ Paris 06, INSERM U1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, Paris, France.
Oriane
O
Trouillard
Department of Neurology, Drammen Hospital, Vestre Viken Hospital Trust, Drammen, Norway.
Jeanette
J
Koht
Child Habilitation Unit, Sørlandet Hospital, Norway.
Thorsten
T
Gerstner
Sørlandet Hospital, Norway.
Siri
S
Moland
Département de Médicine translationnelle et Neurogénétique, IGBMC, CNRS UMR 7104/INSERM U964/Université de Strasbourg, Illkirch, France; Laboratoires de génétique, Institut de génétique médicale d'Alsace, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
Christel
C
Depienne
Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Neurosciences Paris Seine - Institut de Biologie Paris Seine (NPS - IBPS), 75005 Paris, France.
Isabelle
I
Dusart
Sorbonne Universités, UPMC Univ Paris 06, INSERM U1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, Paris, France; Département de Neurologie, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France.
Aurélie
A
Méneret
Département de Neurologie, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France.
Marta
M
Ruiz
Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Neurosciences Paris Seine - Institut de Biologie Paris Seine (NPS - IBPS), 75005 Paris, France.
Caroline
C
Dubacq
Sorbonne Universités, UPMC Univ Paris 06, INSERM U1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, Paris, France; Département de Neurologie, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France.
Emmanuel
E
Roze
Mirror movement; RAD51; corpus callosum; corticospinal tract; motor control; neurodevelopment