Phenotypic Variability of Retinal Disease Among a Cohort of Patients With Variants in the CLN Genes

Abstract

PURPOSE. To describe the phenotype of CLN-associated retinal dystrophy in a subset of patients at the Columbia University Medical Center, United States, and the Hospital das Clínicas de Pernambuco, Brazil, in comparison to the published literature. METHODS. Eleven patients with confirmed biallelic variants in the CLN genes were evaluated via dilated fundus examination, clinical imaging, and full-field electroretinogram. A thorough literature search was conducted to determine previously published variants and associated phenotypes. RESULTS. Genetic testing confirmed the presence of variants in CLN3, CLN7/MFSD8, CLN8, and GRN/CLN11. Five novel variants were identified, and four novel phenotypes of previously published alleles were described. The phenotype differed among patients with variants in the same gene and sometimes among patients with the same allele. CONCLUSIONS. Substantial phenotypic variability among variants in the CLN genes makes identification of genotype–phenotype or allele–phenotype correlations challenging. Further study is required to establish an extensive database for adequate patient counseling.