Exome sequencing reveals PPEF2 variant associated with high myopia

Area of Science:

• Ophthalmology
• Genetics
• Molecular Biology

Background:

• High myopia (HM) is a significant cause of blindness.
• Genetic factors are crucial in HM development.
• Identifying novel genes associated with HM is essential for understanding its pathogenesis.

Purpose of the Study:

• To identify novel genetic variants associated with nonsyndromic high myopia.
• To investigate the role of the PPEF2 gene in HM development.
• To elucidate the functional impact of identified PPEF2 variants.

Main Methods:

• Whole exome sequencing (WES) was employed to screen for variants in a large Uyghur family with HM.
• Sanger sequencing was used to validate variant cosegregation.
• Multiplex PCR targeted amplicon sequencing (MTA-seq) was performed on sporadic HM cases.
• Immunofluorescence (IF) and immunohistochemistry (IHC) assays assessed PPEF2 expression patterns.
• In vitro assays evaluated the functional consequences of the identified variant.

Main Results:

• A novel c.A875G variant in the PPEF2 gene was identified in a Uyghur family with HM.
• The c.A875G variant cosegregated with HM in the family.
• Another novel variant, c.1959C > G, was found in one sporadic HM case.
• PPEF2 is primarily expressed in retinal pigment epithelium, choroid, and retina tissues.
• The c.A875G variant reduced PPEF2 protein levels and impaired cell migration and proliferation while promoting apoptosis.

Conclusions:

• PPEF2 is identified as a novel gene implicated in high myopia.
• The identified PPEF2 variant may cause HM by affecting the migration, proliferation, and apoptosis of relevant cells.
• These findings contribute to understanding the genetic basis of high myopia.