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Specific clinical and brain MRI features in mentally retarded patients with mutations in the Oligophrenin‐1 gene
Author(s) -
Portes Vincent des,
Boddaert Nathalie,
Sacco Silvia,
Briault Sylvain,
Maincent Kim,
Bahi Nadia,
Gomot Marie,
Ronce Nathalie,
Bursztyn Joseph,
Adamsbaum Catherine,
Zilbovicius Monica,
Chelly Jamel,
Moraine Claude
Publication year - 2003
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.20422
Subject(s) - cerebellar vermis , dysgenesis , joubert syndrome , hypotonia , frameshift mutation , medicine , ataxia , pons , atrophy , cerebral atrophy , mutation , pathology , cerebellum , pediatrics , genetics , anatomy , biology , gene , psychiatry
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. © 2003 Wiley‐Liss, Inc.