Table 1.
Overview of RCBTB1 Mutations and the Associated Phenotypes Identified in This Study
| Family | Origin | Mutation (Zygosity) | Individual |
Retinal Phenotype |
Extra-ocular Phenotypic Manifestations | |
|---|---|---|---|---|---|---|
| Age of Onset (Years) | Characteristics | |||||
| F1 | Turkey | c.973C>T (p.His325Tyr) (hom) |
V:1 | 17 | severe iRD compatible with RP | goiter, POI, and mild ID |
| V:2 | 14 | severe iRD compatible with RP | goiter, POI, mild ID, recurrent otitis media, psoriasis, and allergy to house dust mites | |||
| IV:3 | 18 | severe iRD compatible with RP | goiter, POI, and mild ID | |||
| F2 | Italy | c.919G>A (p.Val307Met) (hom) |
II:4 | 40 | progressive pattern-like reticular dystrophy | none reported |
| II:5 | 55 | progressive pattern-like reticular dystrophy | none reported | |||
| F3 | Greece | c.919G>A (p.Val307Met) (hom) |
II:1 | 50 | central chorioretinal atrophy and peripheral reticular dystrophy | thyroid nodules, cold intolerance, and dyslipidemia; son with autism and ID |
| F4 | Greece | c.930G>T (p.Trp310Cys) (hom) |
II:5 | 45 | central chorioretinal atrophy and peripheral reticular dystrophy | sensorineural hearing loss (adult onset) and spinal ganglioglioma |
| III:2 | 30 | central chorioretinal atrophy and peripheral reticular dystrophy | sensorineural hearing loss (adult onset); mother with reported Hashimoto thyroiditis | |||
| F5 | Algeria | c.1151A>G (p.His384Arg) (hom) and c.1202C>T (p.Ser401Leu) (hom) |
II:6 | 48 | progressive pattern-like reticular dystrophy | lung fibrosis |
| F6 | China | c.1164G>T (p.Leu388Phe) (hom) |
II:2 | 33 | retinal dystrophy starting with bilateral vision loss; fundus with bilateral irregular pigmentations mainly in the mid-periphery | none reported |
The phenotypes associated with RCBTB1 mutations vary from a more severe iRD (i.e., RP) and shared extra-ocular features (goiter, POI, and mild ID) in three F1 individuals to progressive iRD with or without extra-ocular features in seven individuals from five families (F2–F6). The clinical onset of iRD in these families is between 30 and 50 years of age, mostly with decreasing visual acuity and an absence of complaints about the peripheral visual field. Fundus pictures show reticular dystrophy in the retinal periphery and rounded spots of chorioretinal macular atrophy, which enlarge with age. Electroretinography is characterized by moderate alterations of all responses (which worsen with age), indicating loss of both rods and cones. Abbreviations are as follows: hom, homozygous; ID, intellectual disability; POI, primary ovarian insufficiency; iRD, inherited retinal dystrophy; and RP, retinitis pigmentosa.