SOBP is mutated in syndromic and nonsyndromic intellectual disability and is highly expressed in the brain limbic system |
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Authors: | Birk Efrat Har-Zahav Adi Manzini Chiara M Pasmanik-Chor Metsada Kornreich Liora Walsh Christopher A Noben-Trauth Konrad Albin Adi Simon Amos J Colleaux Laurence Morad Yair Rainshtein Limor Tischfield David J Wang Peter Magal Nurit Maya Idit Shoshani Noa Rechavi Gideon Gothelf Doron Maydan Gal Shohat Mordechai Basel-Vanagaite Lina |
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Institution: | 1 Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel 2 Division of Genetics, Manton Center for Orphan Diseases and Howard Hughes Medical Center, Children's Hospital Boston, Boston, MA 02115, USA 3 Bioinformatics Unit, G.S.W. Faculty of Life Sciences, Tel-Aviv University, Tel Aviv 69978, Israel 4 Imaging Department, Schneider Children's Medical Center of Israel, Petah Tikva 49202, Israel 5 Section on Neurogenetics, Laboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA 6 Raphael Recanati Genetics Institute, Rabin Medical Center, Beilinson Campus, Petah Tikva 49100, Israel 7 Sheba Cancer Research Center, The Chaim Sheba Medical Center, Tel Hashomer 52621, Israel 8 INSERM U781, Université Paris Descartes, Hôpital Necker-Enfants Malades, 75015 Paris, France 9 Pediatric Ophthalmology Service, Assaf Harofeh Medical Center, Zrifin 73000, Israel 10 The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer 52621, Israel 11 Department of Internal Medicine D, Rabin Medical Center, Beilinson Hospital, Petah Tikva 49100, Israel 12 Felsenstein Medical Research Center, Tel Aviv University, Rabin Medical Center, Beilinson Campus Petah Tikva 49100, Israel 13 Schneider Children's Medical Center of Israel, Petah Tikva, 49202, Israel |
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Abstract: | Intellectual disability (ID) affects 1%-3% of the general population. We recently reported on a family with autosomal-recessive mental retardation with anterior maxillary protrusion and strabismus (MRAMS) syndrome. One of the reported patients with ID did not have dysmorphic features but did have temporal lobe epilepsy and psychosis. We report on the identification of a truncating mutation in the SOBP that is responsible for causing both syndromic and nonsyndromic ID in the same family. The protein encoded by the SOBP, sine oculis binding protein ortholog, is a nuclear zinc finger protein. In mice, Sobp (also known as Jxc1) is critical for patterning of the organ of Corti; one of our patients has a subclinical cochlear hearing loss but no gross cochlear abnormalities. In situ RNA expression studies in postnatal mouse brain showed strong expression in the limbic system at the time interval of active synaptogenesis. The limbic system regulates learning, memory, and affective behavior, but limbic circuitry expression of other genes mutated in ID is unusual. By comparing the protein content of the +/jc to jc/jc mice brains with the use of proteomics, we detected 24 proteins with greater than 1.5-fold differences in expression, including two interacting proteins, dynamin and pacsin1. This study shows mutated SOBP involvement in syndromic and nonsyndromic ID with psychosis in humans. |
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