Modern diagnosis and treatment of Leber congenital amaurosis with CEP290 gene

Purpose. Demonstration of a clinical case of Leber congenital amaurosis. Material and methods. This article presents a clinical case of diagnosing Leber congenital amaurosis in a 5-year-old patient. Results. The disease is caused by biallelic loss-offunction mutations in the CEP290 gene (Leber congenital amaurosis type 10), which leads to dysregulation of metabolism within photoreceptor ciliary transport. A heterozygous mutation in the 26th intron of the CEP290 gene (chr12: 88494960T>C, rs281865192) leads to the formation of an alternative splicing site (c.2991+1655A>G, NM_025114.3), which causes the disease in the child. Conclusion. A defective mutation in the CEP290 gene (mutation p.Cys998X, also known as c.2991+1655A>G) has been reported in 57% of Caucasian patients. Clinical manifestations vary from object vision to complete blindness. The prognosis for the development of visual functions is unfavorable. Diagnosis and treatment pose certain difficulties given the decline in visual function with age. Thanks to modern technologies and the active development of clinical genetics, it becomes possible to successfully resolve this disease thanks to the drug sepofarsen (QR-110), which modulates RNA splicing, thereby blocking access to the active site of cryptic splicing and restoring preference for the CEP290 type splicing site, opening new horizons in the treatment of Leber’s amaurosis type 10. Key words: Leber’s amaurosis type 10, sepofarsen, mutation in the CEP290 gene, p.Cys998X mutation, c.2991+1655A>G mutation For citation: Ermolaeva E.V., Sidorenko E.E., Malinovskaya V.S., Rozmetova B.Sh., Suvorova Yu.A., Krapivkin A.I., Loskutova V.E., Grigoriev G.V. Modern diagnosis and treatment of Leber congenital amaurosis with CEP290 gene. Rossiyskaya detskaya oftalmologiya. 2024;4(50): 27–37.