GPR98 mutations cause Usher syndrome type 2 in males

Area of Science:

• Genetics
• Ophthalmology
• Rare Diseases

Background:

• Mutations in the GPR98 gene are linked to Usher syndrome type 2C (USH2C).
• Previously, all identified USH2C patients were female, leading to speculation of a more severe, potentially lethal, phenotype in males.
• The role of GPR98 in male patients with USH2C remained largely unexplored.

Purpose of the Study:

• To report the first cases of Usher syndrome type 2C (USH2C) in male patients.
• To investigate novel GPR98 mutations in individuals with USH2.
• To re-evaluate the prevalence and clinical spectrum of USH2C in both sexes.

Main Methods:

• Genetic analysis of the GPR98 gene in patients diagnosed with Usher syndrome type 2.
• Clinical characterization of affected individuals, including a male patient and his sister.
• Review of previous literature and case reports concerning GPR98 mutations and USH2C.

Main Results:

• Two male patients with Usher syndrome type 2 (USH2) were identified with novel mutations in the GPR98 gene.
• Clinical evaluation revealed a typical USH2 phenotype in both the male patient and his affected sister.
• These findings indicate that GPR98 mutations are a cause of USH2C in males, presenting with a typical phenotype.

Conclusions:

• GPR98 mutations are implicated in Usher syndrome type 2C (USH2C) in both male and female patients.
• The GPR98 gene should be considered in the genetic investigation of USH2 in patients of both sexes.
• Previous underestimation of USH2C prevalence may be due to the exclusion of males from systematic GPR98 studies.