The contribution of genetic test results to the patient management in an ophthalmology clinic: Results from a Turkish cohort clinically diagnosed as Stargardt disease

Background/aim: The aim of the study was to analyse the genotype and phenotype characteristics of Turkish patients with a clinical diagnosis of Stargardt disease and to evaluate how the teaming between the departments of medical genetics and ophthalmology contributes to patient management. 

Materials and methods: The clinical findings, genetic testing workflow in the medical genetics department, and the genetic testing results of patients clinically diagnosed with Stargardt disease in the ophthalmology department were retrospectively analysed.

Results: The study included 50 patients from 46 families. The genetic test reports confirmed the clinical diagnosis of Stargardt disease type 1 (STGD1) in 27 patients (54%), led to revision of the clinical diagnosis in 5 patients (10%), and were inconclusive in 18 patients (36%). Twenty-six pathogenic ABCA4 variants were reported in 39 patients, three of which were novel: c.466_467dupAT, p.Leu157SerTer2; c.4540-1G>C; c.878delC, p.Met293SerfsTer7.  The most recurrent ABCA4 variant was c.5882G>A, p.Gly1961Glu detected in 10 unrelated patients. Patients with biallelic severe ABCA4 variants or biallelic loss of function variants had an earlier age of ascertainment (p=0.024 and p=0.008, respectively). The mean interval between the referral of patients from the ophthalmology clinic and the first visit with the medical geneticist was 13.8 days and the mean  time to receive genetic test results with post-test counselling was 6.9 months after the first visit.

Conclusion: This study serves as a representative example of how genetic testing and a multidisciplinary approach can contribute to management of inherited eye diseases.  It also reports three novel ABCA4 variants in Turkish patients with Stargardt disease and described genotype-phenotype correlations. However, conducting multicentre studies with larger sample sizes from Turkey will be essential to broaden the spectrum of ABCA4 variants and enhance our understanding of phenotype-genotype relationships.