RGS9 – Bradyopsia

Bradyopsia is a rare autosomal recessive cone dysfunction marked by mild photophobia, normal color vision, and stationary electrophysiologic abnormalities (HP:0030637). In a retrospective series of 8 patients from 7 families, targeted sequencing of RGS9 and R9AP identified a single British male with compound heterozygous RGS9 variants, c.382C>T (p.Arg128Ter) and c.895T>C (p.Trp299Arg), consistent with AR inheritance and the characteristic cone dysfunction phenotype (PMID:19818506). No additional RGS9 segregation was observed.

Affected individuals exhibit severe cone system suppression under photopic conditions with preserved scotopic cone responses, mirroring RGS9’s established role as a GTPase-activating protein for transducin in phototransduction. Biochemical studies delineating the retina-specific RGS9-1 isoform demonstrate accelerated GTP hydrolysis on Galpha_t, supporting a loss-of-function mechanism in bradyopsia (PMID:19818506; PMID:10066255). Although genetic evidence is limited to a single compound heterozygous case, the concordant electrophysiologic and molecular data support the inclusion of RGS9 in diagnostic gene panels for stationary cone dysfunction.

References

• Ophthalmology • 2010 • Novel mutations and electrophysiologic findings in RGS9- and R9AP-associated retinal dysfunction (Bradyopsia) PMID:19818506
• The Journal of neuroscience • 1999 • Cloning and characterization of RGS9-2: a striatal-enriched alternatively spliced product of the RGS9 gene PMID:10066255

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