title: Specific clinical and brain MRI features in mentally retarded patients with mutations in the Oligophrenin-1 gene.
abstract: Oligophrenin-1 (OPHN-1) gene disruption is known as responsible for so called "non-specific" X-linked mental retardation (MR) Billuart et al. [1998: Nature 392:923-926]. In order to search for a possible specific clinical and radiological profile for mutation in the OPHN-1 gene, clinical and 3D brain MRI studies were performed in the two families with a known mutation in OPHN-1 reported so far: a 19-year-old female with an X;12 balanced translocation encompassing OPHN-1, and four affected males of family MRX60 sharing a frameshift mutation in OPHN-1. Clinical data shared by affected individuals were neonatal hypotonia with motor delay but no obvious ataxia, marked strabismus, early onset complex partial seizures, and moderate to severe MR. Brain MRIs performed in three individuals exhibited a specific vermian dysgenesis including an incomplete sulcation of anterior and posterior vermis with the most prominent defect in lobules VI and VII. In addition, a non-specific cerebral cortico-subcortical atrophy was also observed. These clinical and radiological features suggest a distinct clinico-radiological syndrome. These preliminary data need to be confirmed in other families and will be helpful for further targeted mutation screening of the OPHN-1 gene in male patients with similar clinico-radiological features. In addition, OPHN-1 inactivation should be considered as a relevant model of developmental vermis disorganization, leading to a better understanding of the possible role of the cerebellum in MR.
authors.affiliation: Service de Pédiatrie, HCL, Centre Hospitalier Lyon Sud, 69395 Pierre-Bénite, France. vincent.desportes@chu-lyon.fr
authors.forename: Vincent
authors.initials: V
authors.lastname: des Portes
authors.forename: Nathalie
authors.initials: N
authors.lastname: Boddaert
authors.forename: Silvia
authors.initials: S
authors.lastname: Sacco
authors.forename: Sylvain
authors.initials: S
authors.lastname: Briault
authors.forename: Kim
authors.initials: K
authors.lastname: Maincent
authors.forename: Nadia
authors.initials: N
authors.lastname: Bahi
authors.forename: Marie
authors.initials: M
authors.lastname: Gomot
authors.forename: Nathalie
authors.initials: N
authors.lastname: Ronce
authors.forename: Joseph
authors.initials: J
authors.lastname: Bursztyn
authors.forename: Catherine
authors.initials: C
authors.lastname: Adamsbaum
authors.forename: Monica
authors.initials: M
authors.lastname: Zilbovicius
authors.forename: Jamel
authors.initials: J
authors.lastname: Chelly
authors.forename: Claude
authors.initials: C
authors.lastname: Moraine
mesh_terms: D000328:Adult; D002531:Cerebellum / Q000002:abnormalities* / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004827:Epilepsy / Q000150:complications; D005260:Female; D016368:Frameshift Mutation; D020690:GTPase-Activating Proteins / Q000235:genetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D038901:X-Linked Intellectual Disability / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D009123:Muscle Hypotonia / Q000150:complications; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D014786:Vision Disorders / Q000150:complications
chemical_list: D003598:Cytoskeletal Proteins; D020690:GTPase-Activating Proteins; D009687:Nuclear Proteins; C111952:OPHN1 protein, human