A nonsense mutation in S-antigen (p.Glu306*) causes Oguchi disease

Area of Science:

• Ophthalmology
• Genetics
• Molecular Biology

Background:

• Congenital stationary night blindness (CSNB) is an inherited retinal disorder.
• Mizuo-Nakamura phenomenon is a characteristic symptom of Oguchi disease, a form of CSNB.
• Genetic heterogeneity underlies different types of Oguchi disease.

Observation:

• A 15-year-old Pakistani girl presented with CSNB, Mizuo-Nakamura phenomenon, dural sinus thrombosis (DST), thrombocytopenia, and systemic lupus erythematosus (SLE).
• Genetic analysis focused on the S-antigen (SAG) and rhodopsin kinase (GRK1) genes for Oguchi types 1 and 2, respectively.
• The methylenetetrahydrofolate reductase (MTHFR) C677T variation was investigated for its association with hyperhomocysteinemia.

Findings:

• A novel homozygous nonsense mutation (c.916G>T; p.Glu306*) in the SAG gene was identified as the cause of Oguchi type 1.
• The identified SAG mutation was absent or heterozygous in unaffected siblings.
• The MTHFR C677T heterozygous allele was associated with hyperhomocysteinemia in the patient and family members.

Implications:

• This study reports the first Pakistani case of Oguchi type 1 CSNB caused by a novel SAG mutation.
• The findings expand the mutational spectrum of the SAG gene in inherited retinal diseases.
• The neurologic and hematologic conditions observed in the patient are likely unrelated to the SAG gene variant.