PURPOSE: The aim of this study was to determine the molecular genetic basis of an early-onset severe retinal dystrophy in three unrelated consecutive patients of Czech origin and to describe their ocular phenotype. METHODS: DNA samples from two probands were analyzed using a genotyping microarray (Asper) followed by either target analysis of 43 genes implicated in retinal disorders by next generation sequencing or whole-exome sequencing, respectively. The third proband underwent conventional Sanger sequencing of CRB1 based on her ocular findings. RESULTS: All three probands harboured a known disease-causing mutation c.2843G>A; p.(Cys948Tyr) in the CRB1 gene. One individual was homozygous for this mutation, while in the other two probands c.2308G>A; p.(Gly770Ser) and c.3121A>G; p.(Met1041Val) were also identified in the heterozygous state, respectively. Both variants were novel and evaluated by in silico analysis as pathogenic. A false-negative result was observed in one of the two samples examined by the genotyping microarray. Disease onset in all patients was before the age of 7 years. Hypermetropic refractive error, bilateral nummular retinal pigmentation, retinal thickening and cystoid spaces in the macula were observed in two probands, aged 6 and 7 years. The third proband, aged 28 years, had bone spicule-like pigmentary changes associated with increased retinal nerve fiber layer. CONCLUSIONS: The first study reporting on the molecular genetic cause of non-syndromic early-onset severe retinal dystrophy in Czech patients identified one homozygous and two compound heterozygote probands with CRB1 mutations. Retina nerve fibre layer measurements should be considered an integral part of the clinical evaluation of retinal dystrophies. Detailed clinical examination and imaging can both direct molecular screening and help to confirm or refute disease causation of identified variants.

• Klíčová slova
• CRB1, Early-onset retinal dystrophy, Optical coherence tomography, Whole-exome sequencing,
• MeSH
• dědičné nemoci očí diagnóza   genetika   metabolismus   MeSH
• dítě MeSH
• dospělí MeSH
• elektroretinografie MeSH
• fenotyp MeSH
• genotyp MeSH
• homozygot MeSH
• lidé MeSH
• membránové proteiny genetika   metabolismus   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mutace * MeSH
• mutační analýza DNA MeSH
• oční proteiny genetika   metabolismus   MeSH
• proteiny nervové tkáně genetika   metabolismus   MeSH
• retina diagnostické zobrazování   metabolismus   patofyziologie   MeSH
• retinální dystrofie diagnóza   genetika   metabolismus   MeSH
• rodokmen MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• CRB1 protein, human MeSH Prohlížeč
• membránové proteiny MeSH
• oční proteiny MeSH
• proteiny nervové tkáně MeSH

Aim. To evaluate the long-term effect of rheohemapheresis (RHF) treatment of age-related macular degeneration (AMD) on photoreceptor IS/OS junction status. Methods. In our study, we followed 24 patients with dry AMD and drusenoid retinal pigment epithelium detachment (DPED) for a period of more than 2.5 years. Twelve patients (22 eyes) were treated by RHF and 12 controls (18 eyes) were randomized. The treated group underwent 8 RHF standardized procedures. We evaluated best-corrected visual acuity, IS/OS junction status (SD OCT), and macular function (multifocal electroretinography) at baseline and at 2.5-year follow-up. Results. RHF caused a decrease of whole-blood viscosity/plasma viscosity at about 15/12%. BCVA of treated patients increased insignificantly (P = 0.187) from median 74.0 letters (56.2 to 81.3 letters) to median 79.0 letters (57.3 to 83.4 letters), but it decreased significantly from 74.0 letters (25.2 to 82.6 letters) to 72.5 letters (23.4 to 83.1 letters) in the control group (P = 0.041). The mfERG responses in the region of eccentricity between 1.8° and 7° were significantly higher in treated patients (P = 0.04). Conclusions. RHF contributed to sparing of photoreceptor IS/OS junction integrity in the fovea, which is assumed to be a predictive factor for preservation of visual acuity.

• Publikační typ
• časopisecké články MeSH