A nonsense mutation in S-antigen (p.Glu306*) causes Oguchi disease.
OBJECTIVE
Genetic studies were performed to identify the causative mutation in a 15-year-old girl diagnosed with congenital stationary night blindness (CSNB) presenting Mizuo-Nakamura phenomenon, a typical Oguchi disease symptom. The patient also had dural sinus thrombosis (DST), thrombocytopenia, and systemic lupus erythematosus (SLE).


METHODS
Mutation analysis was done by sequencing two candidate genes, S-antigen (SAG; arrestin 1), associated with Oguchi type 1, and rhodopsin kinase (GRK1), associated with Oguchi type 2. In addition, the C677T variation in the methylenetetrahydrofolate reductase (MTHFR) gene was also screened in the family, to determine its probable association with hyperhomocysteinemia in the patient.


RESULTS
Sequencing of the SAG and GRK1 resulted in identifying a novel homozygous nonsense mutation (c.916G>T; p.Glu306*) in SAG, which in unaffected siblings either was present in a heterozygous state or absent. The C677T heterozygous allele in the MTHFR gene was found to be associated with hyperhomocysteinemia in the patient and other family members.


CONCLUSIONS
This is the first report of Oguchi type 1 in a Pakistani patient due to a nonsense mutation (c.916G>T; p.Glu306*) in SAG. The neurologic and hematological abnormalities likely are not associated with the SAG variant.
Shifa College of Medicine, Islamabad, Pakistan.
Nadia K
NK
Waheed
Ahmed H
AH
Qavi
Sarah N
SN
Malik
Maleeha
M
Maria
Moeen
M
Riaz
Frans P M
FP
Cremers
Maleeha
M
Azam
Raheel
R
Qamar
D000293:Adolescent; D000483:Alleles; D019393:Arrestin / Q000235:genetics*; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D015785:Eye Diseases, Hereditary; D005260:Female; D051606:G-Protein-Coupled Receptor Kinase 1 / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000235:genetics; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009755:Night Blindness / Q000150:complications / Q000235:genetics*; D010154:Pakistan; D010375:Pedigree; D035781:Siblings; D012851:Sinus Thrombosis, Intracranial / Q000150:complications / Q000235:genetics
D019393:Arrestin; D018389:Codon, Nonsense; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D051606:G-Protein-Coupled Receptor Kinase 1; C496764:GRK1 protein, human