Mutations of TOPORS identified in families with retinitis pigmentosa

To identify TOPORS mutations in patients with retinitis pigmentosa (RP) from our cohort and summarize the genotypes and phenotypes of TOPORS reported previously.

Probands with RP phenotypes were recruited from our genetic retinopathy screening work. DNA was extracted from the peripheral venous blood, and exome sequencing was performed. We further examined the clinical data and family history in detail in these patients. TOPORS mutations associated with RP were searched and summarized from the previous reports, and the results were combined with the data presented in our study. The mutation spectrum of TOPORS was systematically analyzed, and the phenotypes of truncated mutations and missense mutations were compared and described.

Mutations in TOPORS were detected in three families, including two novel mutations (c.2017C>T, p.Arg673Cys, c.2371A>T, p.Lys791Term) and a known frameshift mutation (c.2554_2557delGAGA, p. Glu852fsTer13). A comprehensive analysis showed that 64.1% (25/39) of the mutant alleles are truncated mutations, and 34.3% (12/39) are missense mutations. About 89.7% (35/39) of the mutations are located in the terminal half of exon 3, which affected the C-terminal of the TOPORS protein. Night blindness was a common onset symptom, and TOPORS-related ERG changes can be observed in early stage. In addition, patients with missense mutations retained better central vision in older age compared to the patients with truncated mutations.

We expand the mutation spectrum and assess the possible genotype-phenotype correlations of TOPORS, which can provide a valuable reference for exploring the pathogenesis of adRP caused by TOPORS mutations.