Page 148 - A Magyar Szemorvostársaság 2023. évi kongresszusa - Tudományos program és előadáskivonatok

Objective: The aim of our study was to analyze the frequency data and phenotypic
characteristics of ABCA4 gene variants and to compare them with those previously described
in scientific literature and by our Ophthalmic Genetics Unit.

Methods: Our study included diagnostic genotyping of more than 300 patients with retinal
dystrophies at the Ophthalmic Genetics Unit of Semmelweis University's Department of
Ophthalmology. Genetic testing was combined with both general as well as disease-specific
ophthalmic and multimodal imaging & functional testing methods.

Results: Among over 300 patients studied, different variants of the ABCA4 gene were detected
in 70 cases that is nearly 1/4 of the patients. In terms of phenotypic appearance our team
identified Stargardt's disease, Fundus Flavimaculatus with macular dystrophy, cone-rod
dystrophy and retinitis pigmentosa. The study identified 13 cases of homozygous and 5 cases
of heterozygous variants for the c.5917del, p.(Val1973*) variant, both leading to severe protein
truncating lesions. The risk factor c.5603A>T, p.Asn1868Ile, known in the scientific literature
as a risk factor, has been identified in 15 cases. In 21 cases, homozygous variations were
detected, and the co-occurrence of 4 and 5 variants was also observed.

Conclusions: The specific mutational mechanisms indicate the severity of the disease
progression, meaning that the cases with multiple variants and certain types of abnormalities
present a more severe phenotypic presentation from a younger age. Results of the studied
cases confirmed the heterogeneous presentation reported in the literature, with the risk
increasing hypomorphic allele also modified the clinical picture in a manner previously
described by previous studies.

The presentation will discuss both the genetic variants identified by our team and the research
efforts to develop a therapeutic target for ABCA4 gene variations.