Establishment of the contribution of AGBL5 in autosomal recessive retinitis pigmentosa: Experience from an Iranian family evaluation and literature review

Abstract

Background

Retinitis Pigmentosa (RP) as inherited disease of the retina causes vision impairment due to progressive abnormalities of photoreceptors or the retinal pigment epithelial cells. RP as a clinical heterogenous disorder characterized by wide genetic heterogeneity with a broad range of causative genes involved in the genesis of the disease. Pathogenic variants in AGBL5 have been reported in few cases with RP. The aim of this study is to identify the accurate clinical diagnosis of RP in an Iranian family based on the combination of clinical and genetic investigations.

Materials and methods

We used whole exome sequencing (WES) to identify the pathogenic genetic defect responsible for RP in an Iranian family with consanguineous marriage. Using various filtering steps, we filtered out the exome data to narrow down the annotated variants. Variant prioritization was done based on a panel of RP genes.

Results

All the annotated variants from WES analysis were passed through various filtering steps depending upon allelic frequency, genomic position, protein impact, pathogenic effect, previous relevance to the disease phenotype and quality of the variants. Finally, we found the nonsense homozygous change in AGBL5 gene (NM_021831.6; c.1729C>T; p.Arg577Ter). The RP phenotypes of the proband were similar to previous reports.

Conclusion

This study can provide further evidence regarding the relationship of pathogenic variants in AGBL5 as a cause of RP and we believe that it can provide evidences for the relationship between clinical manifestations and pathogenic variants.