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

Area of Science:

• Genetics
• Ophthalmology
• Molecular Biology

Background:

• Autosomal dominant retinitis pigmentosa (adRP) is a progressive retinal degeneration.
• Rhodopsin (RHO) gene mutations are a common cause of adRP.

Purpose of the Study:

• To investigate the genetic and clinical features of RHO mutations in Japanese adRP families.
• To analyze the impact of identified RHO mutations on rhodopsin protein conformation.

Main Methods:

• Whole-exome sequencing was performed on ten adRP families.
• RHO mutations were confirmed by Sanger sequencing and cosegregation analysis.
• Ophthalmic examinations and molecular modeling were used to assess phenotypes and mutation impact.

Main Results:

• Two RHO mutations, including a novel one (p.W126L), were identified in two families.
• The novel p.W126L mutation was associated with sector RP phenotype.
• The p.A346P mutation was linked to the classic RP phenotype.
• Molecular modeling suggested p.W126L affects rhodopsin conformation.

Conclusions:

• The novel RHO mutation p.W126L is potentially associated with sector RP.
• Identifying RHO mutations aids in predicting disease severity and providing genetic counseling for adRP.