RHO Mutations (p.W126L and p.A346P)‎ in Two Japanese Families with Autosomal Dominant Retinitis Pigmentosa

Abstract EN

Purpose.

To investigate genetic and clinical features of patients with rhodopsin (RHO) mutations in two Japanese families with autosomal dominant retinitis pigmentosa (adRP).

Methods.

Whole-exome sequence analysis was performed in ten adRP families.

Identified RHO mutations for the cosegregation analysis were confirmed by Sanger sequencing.

Ophthalmic examinations were performed to evaluate the RP phenotypes.

The impact of the RHO mutation on the rhodopsin conformation was examined by molecular modeling analysis.

Results.

In two adRP families, we identified two RHO mutations (c.377G>T (p.W126L) and c.1036G>C (p.A346P)), one of which was novel.

Complete cosegregation was confirmed for each mutation exhibiting the RP phenotype in both families.

Molecular modeling predicted that the novel mutation (p.W126L) might impair rhodopsin function by affecting its conformational transition in the light-adapted form.

Clinical phenotypes showed that patients with p.W126L exhibited sector RP, whereas patients with p.A346P exhibited classic RP.

Conclusions.

Our findings demonstrated that the novel mutation (p.W126L) may be associated with the phenotype of sector RP.

Identification of RHO mutations is a very useful tool for predicting disease severity and providing precise genetic counseling.