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A Chinese family with Oguchi's disease due to compound heterozygosity including a novel deletion in the arrestin gene.

Huang L, Li W, Tang W, Zhu X, Ou-Yang P, Lu G - Mol. Vis. (2012)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Reproductive and Stem Cell Engineering, Central South University, Changsha, PR China.

ABSTRACT

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 NH(2) 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.

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Related in: MedlinePlus

Fundus photographs before and after dark adaption in a Chinese patient with Oguchi’s disease. A: The fundus photographs revealed an abnormal golden-yellow reflex in the light-adapted state. B: This abnormal reflex disappeared after 4 h of dark-adaptation. The left eye is shown.
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f1: Fundus photographs before and after dark adaption in a Chinese patient with Oguchi’s disease. A: The fundus photographs revealed an abnormal golden-yellow reflex in the light-adapted state. B: This abnormal reflex disappeared after 4 h of dark-adaptation. The left eye is shown.

Mentions: The proband was a 13-year-old girl who had night blindness since early childhood. Her BCVA was 1.5 in each eye. The refractive errors were −3.50 −0.50×180° in the right eye and −3.75 −0.50×180° in the left eye. Fundus examinations showed the characteristic golden-yellow discoloration in both eyes and the Mizuo-Nakamura phenomenon, in which the golden-yellow discoloration of the fundus (Figure 1A) disappeared after prolonged dark adaptation (Figure 1B). Neither vascular attenuation nor retinal degeneration was seen throughout the retina, and no maculopathy was observed. The visual fields of both eyes were within normal limits. The full-field scotopic 0.01 ERGs showed undetectable rod b waves in the patient. The scotopic 3.0 ERGs showed a “negative” configuration with a significantly reduced a wave and a nearly absent b wave in both eyes. The photopic 3.0 ERGs and photopic 3.0 flickers seemed almost normal (Figure 2). The girl was the first offspring of an unaffected non-consanguineous couple, and no family history was found in the family pedigree (Figure 3A).


A Chinese family with Oguchi's disease due to compound heterozygosity including a novel deletion in the arrestin gene.

Huang L, Li W, Tang W, Zhu X, Ou-Yang P, Lu G - Mol. Vis. (2012)

Fundus photographs before and after dark adaption in a Chinese patient with Oguchi’s disease. A: The fundus photographs revealed an abnormal golden-yellow reflex in the light-adapted state. B: This abnormal reflex disappeared after 4 h of dark-adaptation. The left eye is shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3298420&req=5

f1: Fundus photographs before and after dark adaption in a Chinese patient with Oguchi’s disease. A: The fundus photographs revealed an abnormal golden-yellow reflex in the light-adapted state. B: This abnormal reflex disappeared after 4 h of dark-adaptation. The left eye is shown.
Mentions: The proband was a 13-year-old girl who had night blindness since early childhood. Her BCVA was 1.5 in each eye. The refractive errors were −3.50 −0.50×180° in the right eye and −3.75 −0.50×180° in the left eye. Fundus examinations showed the characteristic golden-yellow discoloration in both eyes and the Mizuo-Nakamura phenomenon, in which the golden-yellow discoloration of the fundus (Figure 1A) disappeared after prolonged dark adaptation (Figure 1B). Neither vascular attenuation nor retinal degeneration was seen throughout the retina, and no maculopathy was observed. The visual fields of both eyes were within normal limits. The full-field scotopic 0.01 ERGs showed undetectable rod b waves in the patient. The scotopic 3.0 ERGs showed a “negative” configuration with a significantly reduced a wave and a nearly absent b wave in both eyes. The photopic 3.0 ERGs and photopic 3.0 flickers seemed almost normal (Figure 2). The girl was the first offspring of an unaffected non-consanguineous couple, and no family history was found in the family pedigree (Figure 3A).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Reproductive and Stem Cell Engineering, Central South University, Changsha, PR China.

ABSTRACT

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 NH(2) 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.

Show MeSH
Related in: MedlinePlus