Juvenile X-linked retinoschisis (XLRS, MIM#312700) belongs to a group of the vitreoretinal dystrophies. We aimed to describe the phenotype-genotype correlation of three XLRS cases in juveniles with different novel mutations from the Lithuanian population. The patients demonstrated macular retinoschisis and typical cyst-like cavities on spectral-domain optical coherence tomography (SD-OCT) images. The mean central foveal thickness was 569.7 mu m. Two patients presented with peripheral retinoschisis. Flash electroretinogram demonstrated a reduced b/a ratio (T (p.R200L) mutation was detected in one case, showing to be pathogenic in silico analysis. c. (92_97) insC (p.W33fs) mutation was identified for another patient, indicating the variant is possibly damaging in silico analysis. The third case was identified with a pathogenic mutation c.422C>G (p.R141H), HGMD CM981753. These are the first cases of XLRS in the Lithuanian population confirmed by molecular genotyping. Presented patients had a different genotype but similar phenotypic traits.

Variants in COL4A3 and COL4A4 cause autosomal dominant and recessive Alport syndrome, yet data on their distribution and clinical expression in different populations remain limited. This study investigated genotype–phenotype correlations and the distribution of COL4A3/COL4A4 variants in a Lithuanian Alport syndrome cohort. A total of 221 individuals from Lithuania were analyzed for COL4A3 and COL4A4 variants using either next-generation sequencing or Sanger sequencing in order to assess variant distribution and associated clinical features. Only individuals with pathogenic, likely pathogenic, or uncertain significance variants were included. Fifty-two individuals (38 index cases) with pathogenic, likely pathogenic, or variants of uncertain significance were identified, as follows: forty-eight were heterozygous, four had autosomal recessive, and four had digenic Alport syndrome. COL4A3 variants were found in 9.5% (21/221) and COL4A4 in 17.6% (39/221). Among the 28 identified variants, 18 were novel. Glycine substitutions (n = 8) were the most frequent and associated with worse kidney outcomes and increased hearing abnormalities. Hematuria was diagnosed significantly earlier than proteinuria (p = 0.05). Most individuals with autosomal dominant Alport syndrome had normal kidney function (eGFR > 90 mL/min/1.73 m²), while those with autosomal recessive Alport syndrome had more severe disease. Kidney failure occurred in 2/4 (50%) autosomal recessive Alport syndrome and 2/48 (4%) autosomal dominant Alport syndrome cases. A significant inverse correlation was found between eGFR and age in proteinuric individuals (r = –0.737; p = 0.013). This study expands knowledge of Alport syndrome in the Lithuanian population and contributes novel variant data to the global Alport syndrome genetic database.

Background and Objectives: Cuticular drusen are a rare form of early-onset drusen maculopathy, which falls within the spectrum of age-related macular degeneration. Previous research suggests that cuticular drusen can result from monogenic inheritance of pathogenic variants in the complement factor H coding CFH gene. These variants impair regulation of the alternative complement pathway, leading to increased central retinal inflammation, progressive tissue damage, and ultimately, vision loss. This study aims to assess the pathogenic potential of the variant NM_000186.4(CFH):c.1318C>T, previously classified as a variant of unknown significance. Materials and Methods: Eight individuals from three generations of a single family underwent ophthalmologic evaluation, including biomicroscopy, ophthalmoscopy, optical coherence tomography, and optical coherence tomography angiography. Subsequently, whole-exome sequencing of the proband‘s DNA sample was performed. Sanger sequencing was used to validate the whole-exome sequencing results and to assess segregation of the identified variant in the family. The individuals’ clinical, instrumental, and genetic data were collected and stored in the database iGENLIT. Results: the heterozygous NM_000186.4(CFH):c.1318C>T variant was detected in six family members. Of these, five have been clinically diagnosed with cuticular drusen. Three affected individuals are currently in their 40s and maintain good visual acuity. In two family members, the drusen progressed to choroidal neovascularization, fibrosis, and atrophy, resulting in profound visual loss at the ages of 54 and 62. One 21-year-old individual also carries the variant, but currently shows no evidence of drusen, likely due to age. Conclusion: In this study, we demonstrated a genotype–phenotype relationship in individuals with the NM_000186.4(CFH):c.1318C>T variant, which suggests its pathogenic role in the development of cuticular drusen and associated complications.