Purpose To present a previously unreported African American family with 1 variation and 1 mutation of the homeobox transcription factor gene, VSX1 (RINX), and to describe the clinical features of family members. Design Family genotype and clinical studies. Participants A 3-generation family with 7 available family members. Methods Blood was drawn from all available family members, and the VSX1 (RINX) gene was sequenced. Craniofacial abnormalities, central nervous system defects, anterior segment features, and retinal and auditory function were assessed. Main outcome measures Main outcome measures included identification and molecular characterization of 1 variation and 1 mutation in VSX1 (RINX) of 4 affected family members (3 adults and 1 child). Craniofacial features were documented. Central neuroimaging was performed. Ophthalmologic findings were described. Retinal and auditory functions were quantified. Results Two changes in VSX1 (RINX) were identified: a variation (R131S) not in a critical region and in few controls, and a mutation (A256S) in the critical CVC-domain and not in any controls. Both were present on 1 chromosome at 20p11.2 and were segregated with the 4 affected patients. Clinical features demonstrated extremely variable expressivity. Craniofacial features, including wide interpupillary distance and unusual pinnae, occurred in the 4 affected patients. Neuroimaging demonstrated that the propositus had an empty sella turcica, a posterior fossa cyst, an anterior encephalocele, hypertelorism, and severe hydrocephalus; her mother had a partially empty sella turcica, a small pituitary gland without any subarachnoid extension of fluid, and hypertelorism; and her older sister had hypertelorism but otherwise normal neuroimaging results. Anterior segment anomalies of the corneal endothelium were a constant finding in all affected family members. Electrophysiologic examination provided evidence for abnormal cone bipolar cells (visual evoked response and electroretinogram) in the adult affected patients and for abnormal auditory bipolar cells (audiogram and audio-evoked brainstem response) in the propositus. Conclusions The new mutation in the VSX1 (RINX) gene described in this report results in abnormal craniofacial features, absence of the roof of the sella turcica, and anomalous development of the corneal endothelium. This mutation also impacts on the maintenance of cone bipolar cells of the visual system and of bipolar cells of the auditory system.
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