PMC5640518_01
Exam findings for Patient 2. A: Electroretinograms (ERGs) recorded from Patient 2's right eye at 5 months old (black traces). Scotopic and photopic responses closest in flash strength to International Society for Clinical Electrophysiology of Vision (ISCEV) standards are shown. Mixed-response ERGs at 1.3 cd s/m2 are shown instead of at the traditional 3.0 cd s/m2 flash strength. Light-adapted ERGs at 2.25 cd s/m2 are shown instead of at the traditional 3.0 cd s/m2 flash strength. Scotopic ERG testing showed response amplitudes below the 99% prediction interval for normal, with prolonged b-wave implicit times. Photopic function was also significantly attenuated, with b-wave responses below the normal mean for his age by two standard deviations and implicit times prolonged. The amplitude of the 30-Hz flicker response was 10 microV, about 10% of normal. Control ERGs performed at the same institution for a healthy 10-month-old are included for comparison (red traces). DA = dark adapted; LA = light adapted. B: Right and left fundus photographs at age 3 years, showing red foveal areas and increased pigmentation in the parafoveal area. C: Family pedigree of Patient 2. Stripes indicate a maternal aunt with Stargardt disease.
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Photopic function was also considerably attenuated, with b-wave responses below the normal mean for his age by two standard deviations (Figure 2A). At age 3, on a clinical exam, blunted foveal reflexes and a faint bull's eye pattern in the macula were noted but were not evident on fundus photography (Figure 2B). Family history was significant for a maternal aunt with Stargardt disease (Figure 2C).
Schematics. A: Schematic showing the conservation of the amino acid p.(Gly1496Glu) across the genomes of ten species. B: Schematic of the CACNA1F transmembrane protein and the positions of mutations p.(Trp332*) and p.(Gly1496Glu). (Adapted from).
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This position was highly conserved (Figure 3A), and this mutation was predicted to be deleterious (PolyPhen-2, SIFT, Protein Variation Effect Analyzer (PROVEAN), and MutationTaster; Table 1).