Abstract
Purpose :
To report a case of autosomal recessive achromatopsia in a child with a novel homozygous nonsense mutation in PDE6C.
Methods :
A retrospective chart review was performed with over 4 years of clinical follow up. Investigators reviewed the patient’s visual acuity, optical coherence tomography (OCT), full field electroretinography (ffERG), and serial comprehensive ophthalmologic exam results to ascertain patient’s clinical phenotype. The patient underwent genetic testing with an Inherited Retinal Disorders panel (NGS, 248 genes) by Invitae-Spark Therapeutics. Genetic results and counseling were disclosed to the patient’s parents in person during a subsequent clinic visit by an inherited retinal disease specialist.
Results :
A six-year-old male presented with severe photophobia and pendular nystagmus. The patient was born at full term from a consanguineous marriage of two first cousins. Patient’s cycloplegic refraction showed high myopic astigmatism with best corrected visual acuity of 20/150 in both eyes (OU). Dilated fundoscopic examination revealed a mild blunting of the foveal light reflex with subtle subfoveal granular pigmentary changes OU. OCT revealed severe attenuation of the subfoveal outer nuclear layer and punctate disruptions in the ellipsoid zone, both consistent with cone photoreceptor loss. Paucity of panretinal cone photoreceptor function was corroborated by ffERG (sedated), which revealed nonrecordable response to the 30Hz flicker photopic stimuli and severe attenuation of photopic amplitudes; scotopic and maximum combined responses were within normal limits. Due to age, color vision could not yet be performed. Genotyping (NGS) revealed a novel pathogenic nonsense mutation (homozygous) in the PDE6C gene [exon 13, c.1669C>T; p.Arg557*]. The patient has remained clinically stable with serial examination every 4-6 months with no evidence of progression of retinal degeneration by serial OCT imaging.
Conclusions :
The novel homozygous nonsense (null) mutation in PDE6C (p.Arg557*) is consistent with an achromatopsia phenotype. Marked loss of PDE6C protein solely in cone photoreceptors is expected to severely attenuate cone phototransduction and perhaps challenge cone vitality. Replacement gene therapy (prior to cone loss) would be a reasonable approach for null PDE6C-induced achromatopsia phenotype in future clinical trials.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.