Latasiewicz Marta, Salvetti Anna Paola, MacLaren Robert E
a Oxford Eye Hospital , Oxford University Hospitals NHS Foundation Trust , Oxford , UK.
b Nuffield Laboratory of Ophthalmology, University of Oxford , Oxford , UK.
Ophthalmic Genet. 2017 Dec;38(6):562-566. doi: 10.1080/13816810.2017.1313994. Epub 2017 Apr 28.
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.
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.
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.
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.
遗传性视网膜变性是年轻人群中不可治疗性失明的主要原因。使用腺相关病毒（AAV）载体的基因治疗的最新进展增加了在基因缺陷情况下通过基因替代减缓或阻止视网膜变性的可能性。
在本报告中，我们展示了一个常染色体显性遗传性视网膜色素变性家族。对105个目标常见ADRP基因进行了筛查。使用二代测序来鉴定突变，随后通过双向桑格测序进行确认。
鉴定出TOPORS基因的一个新突变，c.2539C>T p.(Arg847Ter)，导致一个提前终止密码子，并提示单倍剂量不足作为病理机制。
由于编码TOPORS的cDNA为3135个核苷酸（在AAV载体的编码能力范围内），且单倍剂量不足是一种与基因表达不足相关的机制，基因替代疗法可能是患有这种疾病患者的一种选择。
