Autosomal dominant occult macular dystrophy with an RP1L1 mutation (R45W)

To characterize clinical features in occult macular dystrophy (OMD) patients with the RP1L1 gene mutation (p.R45W), one of two previously described mutations in Japanese OMD patients.

Mutational screening of the RP1L1 gene was performed via polymerase chain reaction and direct sequencing for seven unrelated probands (one autosomal dominant and six sporadic probands) with OMD. A comprehensive ophthalmic examination was performed, including Cirrus optical coherence tomography. Full-field electroretinography (ERG), multifocal ERG, and focal macular ERG were performed.

The heterozygous mutation (p.R45W) was found in only one female proband with autosomal dominant OMD, whose mother was also diagnosed with OMD and carried the mutation. Ophthalmoscopy showed bilateral normal fundi in the proband but subtle retinal pigment epithelium mottling in the mother. Both the proband and her mother had typical OMD findings: decreased visual acuity and markedly reduced central responses in the multifocal ERG and focal macular ERG. Although full-field ERG revealed normal rod and standard combined responses, photopic and 30-Hz flicker responses were slightly reduced in both the proband and her mother. Optical coherence tomography revealed that the external limiting membrane and inner segment-outer segment boundary were disorganized despite normal macular thickness in the proband, whereas the mother exhibited macular thinning with discontinuous reflectivity of the external limiting membrane and inner segment-outer segment boundary.

The clinical phenotypes differed between the proband and her mother and were indistinguishable from other sporadic or RP1L1-unassociated OMD patients, suggesting that mutation-dependent clinical features may not be present.