Purpose Oguchi’s disease is a rare autosomal recessive disease and known to be caused by mutations in the rhodopsin kinase (GRK1) gene or the arrestin (SAG) gene. SAG contains 16 exons and encodes a protein with 405 amino acids. This study was to identify the underlying genetic defects in a non-consanguineous Chinese family with Oguchi’s disease. Methods Ophthalmologic examinations including fundus photography and electroretinography (ERG) were performed on all family members. All exons of the GRK1 gene and the SAG gene were amplified with PCR and directly sequenced. Quantitative real-time PCR (qPCR) was performed to screen heterozygous deletions/duplications in the SAG gene. Long-range PCR and direct sequencing were further performed to define the breakpoints. Results The patient had characteristic clinical features of Oguchi’s disease, including night blindness, normal vision fields, typical fundus appearance with the Mizuo-Nakamura phenomenon, nearly undetectable rod b waves in the scotopic 0.01 ERGs, and nearly “negative” scotopic 3.0 ERGs. No mutations were found in the GRK1 gene. A heterozygous nonsense Arg193stop (R193X) mutation was found in the SAG gene in the patient and the unaffected mother. No pathogenic SAG mutations were found in the unaffected father. qPCRs showed a heterozygous deletion encompassing exon 2 of the SAG gene in the patient and the unaffected father. Long-range PCR and direct sequencing verified the deletion and revealed the breakpoints of the deletion, skipping a 3,224-bp fragment of the SAG gene. The deletion was not detected in 96 unrelated healthy controls. This deletion was predicted to eliminate the exon 2 and the AUG initiate codon in the mature SAG mRNA and cause no production of the SAG protein or low-level production of a non-functional truncated protein lacking 134 amino acids in the NH2 terminus. Conclusions Compound heterozygosity of a nonsense R193X mutation and a heterozygous deletion of 3,224 bp encompassing exon 2 in the SAG gene is the cause of Oguchi’s disease in this Chinese family. qPCR analysis should be performed if there is a negative result of the mutation screening of the SAG gene in patients with Oguchi’s disease.
