case_images: PMC11775458_01
case_images: Genetic findings in the affected individuals. (a) Pedigree and variant (M) segregation in the reported family. Filled symbols denote affected individuals. The proband (II.3) is indicated by an arrowhead. (b) Sanger sequencing chromatograms of the region spanning the TUBB4B (NM_006088.6):c.1049A>C variant (shaded in grey) from the analyzed family members. The proband (II:3) and her affected son (III:4) are heterozygous for the variant (A/C), whereas her unaffected parents (I:1, I:2) and son (III:3) are homozygous for the reference sequence (A/A). (c) Schematic illustration (not to scale) of the TUBB4B gene and protein structure showing the position of the genetic variants identified to date in cases with sensorineural disease (the identified missense variant is given in bold).
case_images: MGG3-13-e70068-g004.jpg
case_images: PMC11775458_01_MGG3-13-e70068-g004.jpg
case_images: mgg370068-fig-0001
case_images: She had two unaffected brothers and there were no reports of other affected members in the maternal and paternal sides of the family (Figure 1a). The proband had two sons, one who suffered from similar symptoms and one unaffected (Figure 1a). The proband's second child was also affected (Figure 1a).
case_images: Ophthalmological findings in the proband and her affected son. (a, f) Fundus imaging of the affected individuals. The proband (II:3) presented a quite pale optic disc, reduction of retinal vessel size, areas of RPE dystrophy at the posterior pole, and pigment deposits (bone-spicule like and clumps) primarily distributed along the vascular arcades. No pigment deposits were visible in the far periphery and in the central/macular area (a). The proband's affected son (III:4) had a normal fundus, without pigment deposits or evident signs of RPE dystrophy (f). (b, g) Fundus autofluorescence (FAF) imaging. Reduced autofluorescence (AF) and focal areas of definitely decreased AF (DDAF) at the posterior pole were observed in the proband (b). Her son presented an overall normal AF distribution at the posterior pole, with fine stippling of hypoautofluorescent spots around the macular area (g). (c, h) Optical coherence tomography (SD-OCT) imaging. SD-OCT showed reduced macular thickness, RPE dystrophy/atrophy, and vitreoretinal interface syndrome in the proband (c). In her son, a subtle reduction of macular thickness and discontinuous/disrupted ellipsoid zone (EZ) band at the foveal region (red arrows) was observed (h). (d, e, i, j) Scotopic and photopic ERG responses. Patient ERG traces are depicted in blue and normal reference traces in black. The amplitudes of the scotopic ERG responses were subnormal in the proband (approximately 30% lower than the norm) (d) and normal in her son (i), whereas the photopic responses were unrecordable in both (e, j).
case_images: MGG3-13-e70068-g001.jpg
case_images: PMC11775458_01_MGG3-13-e70068-g001.jpg
case_images: mgg370068-fig-0002
case_images: This pattern of pigment distribution was confirmed at the most recent fundus inspection at 46 years (Figure 2a). The involvement of the central retina was more evident in FAF images that showed reduced FAF with focal areas of definitely decreased FAF (DDAF) at the posterior pole, indicative of RPE dystrophy/atrophy at the macular area (Figure 2b). SD-OCT imaging revealed morphological changes in the retinal structure, such as thinning of the central retina, no detectable ellipsoid zone (EZ) band, and atrophy of the RPE (Figure 2c). The scotopic ERG responses, which were initially normal, were still recordable at the latest assessment albeit subnormal (approximately 30% lower than the normal value) (Figure 2d), whereas the photopic ones were not detectable (Figure 2e). The retinography revealed an almost normal fundus, without evident signs of RPE dystrophy or pigment deposits (Figure 2f). FAF imaging showed an overall normal distribution of AF at the posterior pole, with a fine granular pattern of hypoautofluorescent spots (stippling) surrounding the macular area (Figure 2g). SD-OCT showed a mild reduction of macular thickness and a discontinuous/disrupted EZ band at the foveal region (Figure 2h), which is consistent with the reduced visual acuity of the subject. The scotopic ERG responses were normal (Figure 2i), whereas the photopic ones were subnormal (Figure 2j).