Pathogenicity reclassification of the RPE65 c.1580A>G (p.His527Arg) - a case report

ABSTRACT

Background

It is of utmost importance to define the molecular diagnosis of patients with retinitis pigmentosa (RP) due to existing targeted therapeutic option: voretigene neparvovec.

We provide clinical evidence for pathogenicity reclassification of variants of uncertain significance (VUSs) RPE65 c.1580A>G (p.His527Arg).

Materials and Methods

A case report of a 10-year-old boy with progressive vision loss. The patient manifested disease highly suggestive of RPE65 retinal dystrophy: nyctalopia, fairly good central vision, severely depressed full-field electroretinography responses and complete loss of peripheral fundus aut ofluorescence.

Results

Invitae Inherited Retinal Disorders Panel identified likely pathogenic mutation RPE65 c.499G>T (p.Asp167Tyr) and RPE65 c.1580A>G (p.His527Arg), variant of uncertain significance. Segregation analysis confirmed that these variants are in trans.

Conclusions

We conclude that the variant RPE65 c.1580A>G (p.His527Arg) has contributed to the pathologic phenotype, demonstrating its significance clearly in the case presented, and should be reclassified according to the criteria of evidence as pathogenic. Therefore, patients with this specific variant in homozygous or compound heterozygous form would likely benefit from genetic treatment based on recombinant adeno-associated virus vector, providing a working RPE65 gene to act in place of a mutated RPE65 gene.

KEYWORDS:

• Genes
• mutation
• retinitis pigmentosa
• night blindness
• photoreceptor cells

Disclosure statement

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

Ethical considerations

The research adhered to the tenets of the Declaration of Helsinki. Written informed consent for molecular genetic analysis, publication of the patient’s clinical data, photos and genetic results was obtained from the patient’s legal guardian.

Additional information

Funding

The author(s) reported that there is no funding associated with the work featured in this article.