Clinical phenotype in ten unrelated Japanese patients with mutations in the EYS gene

To characterize the clinical phenotypes associated with previously-reported mutations of the eyes shut homolog (EYS) gene, including a truncating mutation, c.4957_4958insA, which is a major causative mutation for retinitis pigmentosa (RP) in Japan.

The study population comprised ten unrelated RP subjects with very likely pathogenic mutations in both alleles, four of them with a homozygous c.4957_4958insA mutation. The phenotype analysis was based on ophthalmic examination, Goldmann perimetry, and digital fundus photography.

The study population included six men and four women aged 34-74 years. The average age at first visit was 31 years (range, 14-44 years), and the patients typically presented with night blindness as the initial symptom and subsequently developed progressive constriction of the visual field. Myopia was noted in 9/20 affected eyes. For most patients, central visual acuity was preserved relatively well up to their thirties, after which it deteriorated rapidly over the next two decades. The visual acuity of patients homozygous for the c.4957_4958insA mutation was uniform. Visual fields were constricted symmetrically, and the extent of constriction seemed to be better correlated with age than visual acuity. The fundus displayed bone spicules, which increased in density with age, and attenuated retinal vessels.

Although additional studies with more patients with mutations of the EYS gene are required, it appears that patients share a relatively uniform phenotype with near-normal central visual function up to their twenties. The patients homozygous for the c.4957_4958insA mutation showed a uniform course of visual acuity changes.