RESUMO
Background: The complete form of X-linked congenital stationary night blindness (CSNB1A) is a very rare genetic disease caused by mutation in the NYX gene. CSNB1A-associated several mutations in the NYX gene have been reported earlier.Methods: In this case report, we have clinically diagnosed and genetically confirmed a novel mutation associated with CSNB1A in four members of a Russian family. Two male siblings from a family of four siblings (two girls, two boys) with non-progressive stable night blindness since early childhood and high myopia underwent - visual acuity test, perimetry, biomicroscopy, OCT, ophthalmoscopy, electroretinography, color vision Hue test, NGS based whole exome analysis and Sanger sequencing for clinical characterization and genetic confirmation of CSNB.Results: The members are clinically diagnosed and genetically confirmed with CSNB1A. All the patients had a novel frameshift mutation in the NYX gene (c.283delC, p.His95fs, NM_022567.2) that is found to segregate in X-linked mannerConclusions: This is probably the first case report with a novel mutation from Russia associated with CSNB1A.
Assuntos
Oftalmopatias Hereditárias/genética , Oftalmopatias Hereditárias/patologia , Mutação da Fase de Leitura , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Miopia/genética , Miopia/patologia , Cegueira Noturna/genética , Cegueira Noturna/patologia , Proteoglicanas/genética , Adolescente , Idoso , Criança , Feminino , Genótipo , Humanos , Masculino , Linhagem , Prognóstico , Federação RussaRESUMO
ABCA4-associated mutation screening is extensively performed in European, African, American and several other populations for various retinopathies. However, it has not been well studied in a Russian cohort. Using next-generation (325 genes inherited disease panel) and Sanger sequencing technologies for the first time we documented the spectrum of genetic variations in a Russian retinopathy cohort of 51 patients from 10 ethnic groups. We found ABCA4 variations in 70.5% cases and one case with BEST1 variation. Multiple ABCA4 variations, ABCA4 + RDH12, and ABCA4 + BEST1 variations are also observed and the disease severity is found proportionate to the variation burden. Ten novel ABCA4 variations are detected of which 8 belongs to non-Slavonian population. Most of the detected known variations are found in European and American Stargardt disease populations. No retinopathy causing variation is detected in 14 (27%) cases suggesting that in this Russian retinopathies cohort the causal variants could be in genes that are not covered by our 325 gene panel. Therefore, whole genome/exome analysis is required to identify novel retinopathy associated genes and provide better disease management for this heterogeneous cohort.
