RPE65 c.393T>A, p.(Asn131Lys): Novel Sequence Variant Detected. (1st April 2022)

• Record Type: Journal Article
• Authors: Bjeloš, Mirjana; Bušić, Mladen; Ćurić, Ana; Bosnar, Damir; Šarić, Borna; Marković, Leon; Elabjer, Biljana Kuzmanović; Rak, Benedict
• Other Names: Falsini Benedetto Academic Editor.
• Is Part Of: Case reports in ophthalmological medicine. Volume 2022(2022)
• Publication Date: 2022-04-01
• Subjects: Ophthalmology -- Periodicals; Eye -- Diseases -- Periodicals; Ophthalmology; Eye Diseases; Eye -- Diseases; Ophthalmology; Electronic journals; Periodicals; Periodicals; Case Reports; Fulltext; Internet Resources; Periodicals; 617.7
• DOI: 10.1155/2022/5710080
• Languages: English
• ISSNs: 2090-6722

Abstract

Abstract : Background . Leber congenital amaurosis (LCA) is a monogenic, but genetically heterogenous disease, and at least 27 genes are implicated. This case report is aimed at providing evidence to link the novel variant RPE65 c.393T>A, p.(Asn131Lys), variant of uncertain significance (VUS), to clinical phenotype and to set the ground for objective assignment of pathogenicity confidence. Case Presentation . A case report of a female patient with LCA who manifested with nystagmus, night blindness, profound visual deficiency, and peripheral involvement of the retina consistent with RPE65 dystrophy. A thorough clinical examination, diagnostic evaluation, and genetic testing were performed. The patient was a compound heterozygote in trans form: RPE65 c.304G>T, p.(Glu102∗ ) pathogenic, and RPE65 c.393T>A, p.(Asn131Lys), VUS. The latter variant is absent in healthy controls and is considered harmful on in silico prediction. Conclusions . We conclude that RPE65 c.393T>A, p.(Asn131Lys) contributed to the pathologic phenotype, demonstrating its significance clearly in the case presented, and should be reclassified according to the criteria of evidence as likely pathogenic. This being the case, patients with this specific variant are likely candidates for genetic treatment.