R9AP – Bradyopsia

Bradyopsia is a stationary cone dysfunction disorder characterized by slow recovery of photoreceptor responses and mild photophobia. RGS9BP (encoding R9AP) has been implicated in autosomal recessive Bradyopsia through impairment of the RGS9–R9AP complex required for rapid G-protein deactivation.

Genetic evidence from a retrospective series of eight patients identified R9AP mutations in three individuals from two families. A homozygous in-frame deletion, c.94_102del (p.Asp32_Gln34del), was found in two affected sisters and a homozygous frameshift, c.614dup (p.Cys206fs), in a simplex case (PMID:19818506).

Inheritance is autosomal recessive with segregation of the c.94_102del (p.Asp32_Gln34del) variant in the affected siblings (2 affected relatives) (PMID:19818506).

Functional assessments demonstrated concordant electrophysiologic findings: severe cone system dysfunction under photopic conditions with normal scotopic red‐flash responses, consistent with loss‐of‐function of R9AP in cone deactivation (PMID:19818506).

Integration of genetic segregation in a multiplex family, multiple unrelated probands, and consistent electrophysiology supports a moderate association between RGS9BP and bradyopsia. No conflicting reports have been described.

Key take-home: RGS9BP mutation screening is recommended in patients with characteristic electrophysiologic cone dysfunction for diagnosis and genetic counseling.

References

• Ophthalmology • 2010 • Novel mutations and electrophysiologic findings in RGS9- and R9AP-associated retinal dysfunction (Bradyopsia) PMID:19818506

Evidence Based Scoring (AI generated)