A founder mutation in CERKL is a major cause of retinal dystrophy in Finland.

Objective: To study the genetic aetiology of retinal dystrophies (RD) in Finnish patients.

Methods: A targeted next-generation sequencing (NGS) panel of 105 retinal dystrophy genes was used in a cohort of 55 RD patients.

Results: The overall diagnostic yield was 60% demonstrating the power of this approach. Interestingly, a missense mutation c.375C>G p.(Cys125Trp) in the CERKL gene was found in 18% of the patients in either a homozygous or compound heterozygous state. Data from Exome Aggregation Consortium (ExAC) Browser show that the CERKL c.375C>G p.(Cys125Trp) allele is enriched in the Finnish population and thus is a founder mutation. Furthermore, we report the clinical picture of 18 patients with mutations in the CERKL gene. CERKL mutations cause a macular-onset disease, in which symptoms first become apparent at the second decade. We also detected other novel founder mutations in the CERKL, EYS, RP1, ABCA4 and GUCY2D genes.

Conclusions: Our report indicates that the first diagnostic test for Finnish patients with sporadic or autosomal recessive RD should be a targeted test for founder mutations in the CERKL, EYS, RP1, ABCA4 and GUCY2D genes. These results confirm the utility of NGS-based gene panels as a powerful method for mutation identification in RD, thus enabling improved genetic counselling for these families.