PMC8487392_01
The ophthalmologic examination data of the proband. (a) Photograph showing the hair color of the proband. (b) Photograph showing the eye position of the proband. (c) Iris transillumination. Proband's iris with transillumination defects. (d) Fundus examination showing retinal pigmentation due to patchy areas lacking retinal pigment epithelium. (e) OCT examination showing locally thickened retinal epithelium in the macular area and disappearance of fovea structure.
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The proband (IV-3), a 65-year-old man, presented with gray hair (Figure 2(a)), esotropia (Figure 2(b)), albinism of iris edges (Figure 2(c)), decreased visual acuity, congenital nystagmus, and hemorrhagic diathesis. Ophthalmologic examination showed decreased visual acuity (left 0.2 and right 0.3) and a patchy pattern caused by retinal pigmentation (Figure 2(d)). Optical coherence tomography (OCT) demonstrated locally thickened retinal epithelium in the macular area and disappearance of the foveal structure of both eyes (Figure 2(e)).
Genetic analysis of the family. (a) Sanger DNA sequencing chromatogram demonstrates the homozygosity for the mutation (c.1231dupG) of HPS3 in the proband. (b) Real-time PCR detects the expression of HPS3 in the skin biopsy of IV-4, IV-1, and IV-3.
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Among these five homozygous mutations, only the frameshift mutation (NM_032383.5, c.1231dupG/p.D411GfsX32) of HPS3 was associated with the proband's phenotypes (Figure 3(a)). After reverse transcription PCR, real-time PCR detection found that, compared with the healthy controls, the mRNA level of HPS3 was decreased by approximately 30% in the heterozygous carrier and 90% in the homozygous mutation carrier (Figure 3(b)).