Mutations in VMD2 Cause Autosomal Dominant Vitreoretinochoroidopathy (ADVIRC)

Abstract

Abstract: : Purpose: To describe the probable mechanism of specific mutations in VMD2 leading to ADVIRC, and to illustrate the clinical and electrophysiological phenotype in such patients. ADVIRC is a rare retinal dystrophy accompanied by defects in ocular development. Methods: Forty–one affected individuals of 5 large ADVIRC families were clinically examined. In the majority of these additional electrophysiological evaluation was performed, including electro–oculography (EOG) and electroretinography (ERG). Linkage analysis suggested that the gene responsible for ADVIRC is located on chromosome 11q12.3. Mutation detection analysis in the VMD2 gene was performed in all patients. Results: Mutations in VMD2 were identified in all 5 families, which result in simultaneous missense substitutions and exon skipping in each individual. All patients (100%) had the characteristic hyperpigmented retinal band from equator to ora serrata. In 83% of them microcornea was noted. About 56% of patients had vitreous abnormalities, cells in the vitreous were seen in 25%. In 54% of patients the anterior chamber was shallow. A significantly reduced Arden–De Rouck ratio on EOG was noted in 100% of patients, frequently well before ERG responses were reduced. The ERG was abnormal in 77% of patients. Conclusions: Mutations in VMD2 are the underlying cause in ADVIRC. The clinical phenotype of ADVIRC is that of a variably severe chorioretinal dystrophy in combination with ocular develop–mental defects. The EOG is abnormal early during the course of the disease and prior to ERG abnormalities.

Keywords: retinal degenerations: hereditary • degenerations/dystrophies • electrophysiology: clinical