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

ABSTRACT

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.

KEYWORDS:

• Autosomal dominant retinitis pigmentosa
• haploinsufficiency
• TOPORS gene

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Supplemental data

Supplemental data for this article can be accessed on the publisher’s website at http://dx.doi.org/10.1080/13816810.2017.1313994.