SOBP Is Mutated in Syndromic and Nonsyndromic Intellectual Disability and Is Highly Expressed in the Brain Limbic System

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 te...

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Bibliographic Details
Published in:American journal of human genetics 2010-11, Vol.87 (5), p.694-700
Main 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
Format: Article
Language:English
Subjects:
Adult and adolescent clinical studies
Amino Acid Sequence
Animals
Base Sequence
Biological and medical sciences
Carrier Proteins - genetics
Female
Fundamental and applied biological sciences. Psychology
Gene expression
General aspects. Genetic counseling
Genetics
Genetics of eukaryotes. Biological and molecular evolution
Human genetics
Humans
Intellectual deficiency
Intellectual disabilities
Intellectual Disability - genetics
Karyotyping
Life Sciences
Limbic System - metabolism
Male
Medical genetics
Medical sciences
Metalloproteins - genetics
Mice
Molecular and cellular biology
Mutation
Nuclear Proteins - genetics
Pedigree
Proteins
Proteomics
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Psychotic Disorders - genetics
Ribonucleic acid
RNA
Rodents
Studies
Syndrome
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Summary: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.
ISSN:0002-9297
1537-6605
DOI:10.1016/j.ajhg.2010.10.005