Challenges of Phenotype-Genotype Correlations in Rare Diseases

To the Editor We were interested to read the recent article by Smirnov et al.¹ This excellent article described ophthalmologic phenotypes in CLN3 disease. It also raised important questions about prior reports of genotype-phenotype associations in CLN3 disease.

The authors nicely illustrate the complexity of genotype-phenotype associations in CLN3 disease (Figure 3¹). However, some of the information included from the literature did not match our understanding of those same publications.