Oligophrenin-1 (Ophn1) is expressed in mouse retinal vessels.

The Rho GTPase activating protein (RhoGAP) Oligophrenin 1 (Ophn1) regulates numerous members of the Rho family that are involved in neuronal morphogenesis of the central and peripheral nervous system. In the present study we investigated the spatial and temporal expression of Ophn1 in the mouse eye. The expression of Ophn1 was analysed on both mRNA and protein level. To identify the Ophn1 transcripts, adult retina and cerebrum (positive control) of postnatal day (P) 158 was subjected to reverse transcription polymerase chain reaction (RT-PCR) and sequencing of the amplified cDNA. The Ophn1 protein was analyzed in adult retina by Western blotting and in developing eyes at embryonic day (E) 12, E14, E16, E18, P0, P3, P7, P14 and P158 by immunohistochemistry. Ophn1 transcripts were detected in adult retina by RT-PCR and confirmed by sequencing. Western blot analysis revealed the expression of Ophn1 protein in the adult retina. Immunohistochemical examination of developing eyes localized the protein to retinal vasculature with an onset of Ophn1 expression from P14 onwards. The specific expression pattern suggests that Ophn1 could have a physiological role in the retinal vasculatures. At P14, the vessel development in the retina is widely completed, implying that Ophn1 has either a function during adulthood or for the generation of the intermediate plexus during the late vessel development of the retina.

Genotype-phenotype correlation in eight new patients with a deletion encompassing 2q31.1.

Microdeletions of the 2q31.1 region are rare. We present the clinical and molecular findings of eight previously unreported patients with overlapping deletions in 2q31.1. The patients have a variable clinical phenotype and present with developmental delay (7/8), growth retardation (5/8), seizures (2/8) and a craniofacial dysmorphism consisting of microcephaly (4/8), short palpebral fissures (7/8), broad eyebrows with lateral flare (7/8), low-set ears with thickened helices and lobules (5/8), and micrognathia (6/8). Additional congenital anomalies were noted, including limb abnormalities (8/8), heart defects (3/8), genital anomalies (3/8), and craniosynostosis (1/8). Six of these microdeletions, ranging in size from 1.24 to 8.35 Mb, were identified by array CGH, one larger deletion (19.7 Mb) was detected by conventional karyotyping and further characterized by array CGH analysis. The smallest region of overlap in all eight patients spans at most 88 kb and includes only the WIPF1 gene. This gene codes for the WAS/WASL interacting protein family member 1. The patients described here do not present with clinical signs of the Wiskott-Aldrich syndrome and the deletion of this single gene does not allow explaining the phenotype in our patients. It is likely that the deletion of different but overlapping sets of genes from 2q31 is responsible for the clinical variability in these patients. To further dissect the complex phenotype associated with deletions in 2q31, additional patients with overlapping phenotypes should be examined with array CGH. This should help to link particular phenotypes to specific genes, and add to our understanding of the underlying developmental processes.