1Am. J. Med. Genet. B Neuropsychiatr. Genet. 2011 Jan 156B: 67-71
TitleAssociation of RANBP1 haplotype with smooth pursuit eye movement abnormality.
Abstractschizophrenia is a multifactorial disorder and smooth pursuit eye movement (SPEM) disturbance is proposed as one of the most consistent neurophysiological endophenotype in schizophrenia. The aim of this study was to examine the genetic association of RANBP1 polymorphisms with the risk of schizophrenia and with the risk of SPEM abnormality in schizophrenia patients in a Korean population. Two SNPs of RANBP1 were genotyped by TaqMan assay. Their genetic effect of single/haplotype polymorphisms on the risk of schizophrenia and SPEM abnormality from 354 patients and 396 controls were performed using ? and multiple regression analyses. Although no RANBP1 polymorphisms were associated with the risk of schizophrenia, a common haplotype, RANBP1-ht2 (rs2238798G-rs175162T), showed significant association with the risk of SPEM abnormality among schizophrenia patients after multiple correction (P(corr) ?=?0.002-0.0003). The results of present study provide the evidence that RANBP1 on 22q11.21 locus might be causally related to the SPEM abnormality rather than the development of schizophrenia.
SCZ Keywordsschizophrenia
2Cereb. Cortex 2015 Oct 25: 3977-93
TitleRanbp1, Deleted in DiGeorge/22q11.2 Deletion Syndrome, is a Microcephaly Gene That Selectively Disrupts Layer 2/3 Cortical Projection Neuron Generation.
AbstractRANBP1, a Ran GTPase-binding protein implicated in nuclear/cytoplasmic trafficking, is included within the DiGeorge/22q11.2 Deletion Syndrome (22q11.2 DS) critical region associated with behavioral impairments including autism and schizophrenia. RANBP1 is highly expressed in the developing forebrain ventricular/subventricular zone but has no known obligate function during brain development. We assessed the role of RANBP1 in a targeted mouse mutant. RANBP1(-/-) mice are not recovered live at birth, and over 60% of RANBP1(-/-) embryos are exencephalic. Non-exencephalic RANBP1(-/-) embryos are microcephalic, and proliferation of cortical progenitors is altered. At E10.5, radial progenitors divide more slowly in the Ranpb1(-/-) dorsal pallium. At E14.5, basal, but not apical/radial glial progenitors, are compromised in the cortex. In both E10.5 apical and E14.5 basal progenitors, M phase of the cell cycle appears selectively retarded by loss of Ranpb1 function. RANBP1(-/-)-dependent proliferative deficits substantially diminish the frequency of layer 2/3, but not layer 5/6 cortical projection neurons. RANBP1(-/-) cortical phenotypes parallel less severe alterations in LgDel mice that carry a deletion parallel to many (but not all) 22q11.2 DS patients. Thus, RANBP1 emerges as a microcephaly gene within the 22q11.2 deleted region that may contribute to altered cortical precursor proliferation and neurogenesis associated with broader 22q11.2 deletion.
SCZ Keywordsschizophrenia