SOBP is mutated in syndromic and nonsyndromic intellectual disability and is highly expressed in the brain limbic system

Efrat Birk, Adi Har-Zahav, Chiara M. Manzini, Metsada Pasmanik-Chor, Liora Kornreich, Christopher A. Walsh, Konrad Noben-Trauth, Adi Albin, Amos J. Simon, Laurence Colleaux, Yair Morad, Limor Rainshtein, David J. Tischfield, Peter Wang, Nurit Magal, Idit Maya, Noa Shoshani, Gideon Rechavi, Doron Gothelf, Gal MaydanMordechai Shohat, Lina Basel-Vanagaite*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)694-700
Number of pages7
JournalAmerican Journal of Human Genetics
Volume87
Issue number5
DOIs
StatePublished - 12 Nov 2010

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