A novel mutation in the dominantly inherited TOPORS gene supports haploinsufficiency as the mechanism of retinitis pigmentosa.

BACKGROUND: Inherited retinal degenerations are a major cause of untreatable blindness in the younger age group. Recent advances in gene therapy using adeno-associated viral (AAV) vectors have raised the possibility of slowing or stopping retinal degenerations with gene replacement in cases of gene deficiency.

MATERIALS AND METHODS: In this report, we present a family with autosomal dominant retinitis pigmentosa. A screen for common ADRP genes was performed with 105 genes targeted. Next generation sequencing was used to identify the mutation which was next confirmed by bidirectional Sanger sequencing.

RESULTS: A novel mutation of the TOPORS gene was identified, c.2539C>T p.(Arg847Ter), resulting in a premature termination codon and suggesting haploinsufficiency as the pathological mechanism.

CONCLUSIONS: Since the cDNA encoding TOPORS is 3,135 nucleotides (within the coding capacity of AAV vectors) and haploinsufficiency is a mechanism relating to inadequate gene expression, gene replacement therapy may be an option for patients with this condition.