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

ABSTRACT

Background

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 BEST1 gene and its phenotype in the case’s relatives, shedding light on the structural and functional intricacies underlying this rare ophthalmologic disorder.

Case Presentation

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 BEST1, 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.

Conclusions

This case report provides the first clinical description of the c.1101–1 G>T mutation in the BEST1 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.

Abbreviation: ADVIRC : autosomal dominant vitreoretinochoroidopathy; RNA : ribonucleic acid; RPE : retinal pigment epithelium.

KEYWORDS:

• ADVIRC
• BEST1
• genotype-phenotype correlation
• case report

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors’ contributions

AM wrote the manuscript, CMD and AP performed the genetic analysis and were contributor in writing the manuscript, FB, LB and HM acquired and interpreted data, XZ provided data and helped to draft the revised manuscript, GLM contributed to design the work and substantively revised it. All authors reviewed and approved the manuscript. All authors agree to be accountable for all aspects of the work.

Ethics approval and consent to participate

The patient and her relatives gave informed consent for publication; all research have been performed in accordance with the principles stated in the Declaration of Helsinki.

Consent for publication

The patient and her relatives gave written informed consent for publication.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/13816810.2024.2368797.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.