Progression of retinal pigment epithelial alterations during long-term follow-up in female carriers of choroideremia and report of a novel CHM mutation.

Objectives: To report clinical and functional findings in 2 female carriers of choroideremia who were followed up for 11 and 17 years and who showed progression of fundus alterations; and to report a novel CHM mutation.

Methods: We performed follow-ups in 2 female carriers of choroideremia, including repeated clinical and electrophysiologic examinations and fundus autofluorescence. Molecular analysis of the CHM gene was done by direct sequencing of the coding exons.

Results: Follow-up of female carrier 327 took place during 17 years. A second female carrier (subject 869) with a novel gene mutation in CHM was followed up for 11 years. The 2 carriers showed marked pigmentary alterations in the periphery of the retina. At the initial visit, carrier 869 had multiple small, yellowish flecks in the macula. Both carriers developed subnormal 30-Hz flicker responses on full-field electroretinography during follow-up, whereas electrooculography responses were normal. In both carriers, progression of fundus alterations was noted. Fundus autofluorescence images showed multiple small flecks with reduced autofluorescence.

Conclusions: Over time, fundus alterations in female carriers of choroideremia are visible, and mild cone dysfunction might develop. Multiple yellowish flecks can exist in the macula. The typical mottled irregularity in fundus autofluorescence is a valuable diagnostic criterion that facilitates specific genetic testing. Clinical Relevance Fundus alterations in female carriers of choroideremia can progress over time and a mild generalized cone dysfunction can develop. Characteristic irregularities are seen in fundus autofluorescence imaging, which is helpful in identifying female carriers of choroideremia.