Variable expressivity of the autosomal dominant vitreoretinochoroidopathy (ADVIRC) phenotype associated with a novel variant in BEST1

• Published in: Ophthalmic genetics 2024-10, Vol.45 (5), p.470-475
• Main Authors: Mainguy, Adam, Dhaenens, Claire Marie, Poncet, Anais, Billaud, Fanny, Giraud, Lyse, Zanlonghi, Xavier, Masse, Hélène, Le Meur, Guylène
• Format: Article
• Language: English
• Subjects: Adult; Bestrophins - genetics; Chloride Channels - genetics; Choroid Diseases - diagnosis; Choroid Diseases - genetics; Eye Diseases, Hereditary - diagnosis; Eye Diseases, Hereditary - genetics; Eye Proteins - genetics; Female; Fluorescein Angiography; Genes, Dominant; Humans; Mutation; Pedigree; Phenotype; Retinal Degeneration; Retinal Diseases - diagnosis; Retinal Diseases - genetics; Retinal Diseases - pathology; Tomography, Optical Coherence; Visual Acuity - physiology; Visual Fields - physiology
• ISSN: 1381-6810; 1744-5094; 1744-5094
• DOI: 10.1080/13816810.2024.2368797

This case report explores the relationship between genetics and phenotypic variability in autosomal dominant vitreoretinochoroidopathy (ADVIRC). The study focuses on a case presenting a novel mutation in the gene and its phenotype in the case's relatives, shedding light on the structural and functional intricacies underlying this rare ophthalmologic disorder. A 33-year-old female presented for consultation with a history of bilateral retinal damage accompanied by a complaint of decreased visual acuity, progressive visual field deficit, and night blindness over the past year. Ophthalmic examination revealed a distinctive phenotype, including fibrillar vitreous, pigmented cells, and atrophic hyperpigmented retina in the periphery which was suggestive of a diagnosis of ADVIRC. Genetic testing revealed a heterozygous c.1101-1 G>T variant in , a novel splice site mutation. Functional analysis confirmed its impact on pre-mRNA splicing, resulting in an in-frame deletion (p(Ser367_Asn579del)). Family investigation revealed varying degrees of ophthalmologic impairment in the patient's mother and half-sister, both carrying the same mutation. This case report provides the first clinical description of the c.1101-1 G>T mutation in the gene associated with ADVIRC. The presence of intrafamilial variability, as evidenced by the differing clinical features observed in the index case and her half-sister, suggests the potential involvement of mechanisms influencing phenotype expression. : ADVIRC : autosomal dominant vitreoretinochoroidopathy; RNA : ribonucleic acid; RPE : retinal pigment epithelium.