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This Article Figures Only Full Text Full Text (PDF) CME: Take the course for this article: Volume 65, Number 9, November 08, 2005 Data Supplement All Versions of this Article: 01.wnl.0000182813.94713.eev1 65/9/1364    most recent Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zanni, G. Articles by Chelly, J. Search for Related Content PubMed PubMed Citation Articles by Zanni, G. Articles by Chelly, J. Related Collections All Pediatric Developmental disorders Mental retardation All Genetics

Oligophrenin 1 mutations frequently cause X-linked mental retardation with cerebellar hypoplasia

From the University of Paris 5 René Descartes (Drs. Zanni, Billuart, Beldjord, and Chelly, Y. Saillour, M. Nagara, and L. Castelnau), INSERM Unité 567, CNRS UMR8104, Paris, France; Service de Génétique (Dr. Moraine), Hôpital Bretonneau, INSERM U 316, CHU de Tours, Centre de Génétique (Dr. Faivre), Service de Pédiatrie, CHU Dijon, Department of Neurosciences (Drs. Zanni and Bertini), Unit of Molecular Medicine Ospedale Pediatrico Bambi Gesù, Rome Italy; Department of Human Genetics (Dr. Kleefstra), University Medical Centre Nijmegen, The Netherlands; Départment de Génétique (Dr. Durr), INSERM U 289, Hôpital de la Salpêtrière, Paris, France; Service de Génétique (Dr. Guichet), CHU d’ Anger, France; Service de Neuropédiatrie (Dr. Rodriguez), Hôpital Armand-Trousseau, Paris, France; and Service de Neruopédiatrie (Dr. des Portes), Centre Hospitalier Lyon-Sud, France.

Address correspondence and reprint requests to Dr. J. Chelly, Institut Cochin, INSERM U567 24, rue du Fg St Jacques, 75014 Paris, France; e-mail: chelly{at}cochin.inserm.fr

Background: Mutations of oligophrenin 1, one of the first genes identified in nonspecific X-linked mental retardation (MRX), have been described in patients with moderate to severe cognitive impairment and predominant cerebellar hypoplasia, in the vermis.

Objective: To further delineate the phenotypic and mutational spectrum of the syndrome, by screening oligophrenin 1 in two cohorts of male patients with mental retardation (MR) with or without known posterior fossa anomalies.

Methods: Clinical examination, cognitive testing, MRI studies, and mutational analysis (denaturing gradient gel electrophoresis and direct sequencing) on blood lymphocytes were performed in 213 unrelated affected individuals: 196 patients classified as MRX and 17 patients with MR and previously detected cerebellar anomalies.

Results: Four novel oligophrenin 1 mutations were identified. In the MRX group, two nonsense mutations were detected. In the MR group, two mutations were found: a deletion of exons 16 to 17 and a splice site mutation. All patients shared characteristic clinical, radiologic, and distinctive features with a degree of intrafamilial variability in motor and cognitive deficits.

Conclusions: Oligophrenin 1 mutations were found in 12% (2/17) of individuals with mental retardatin and known cerebellar anomalies and in 1% (2/196) of the X-linked mental retardation group.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the November 8 issue to find the title link for this article.

Editorial, see page 1346

This article was previously published in electronic format as an Expedited E-Pub at www.neurology.org.

Supported by Institut National de la Santé et de la Recherche Scientifique (INSERM), Italian Telethon (project 492/B), European Community (QLG3-CT-2002-01810), Fondation pour la Recherche Médicale, and the Fondation Jerôme Lejeune.

*Both authors contributed equally to the manuscript.

Disclosure: The authors report no conflicts of interest.

Received February 1, 2005. Accepted in final form July 19, 2005.

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