Phenotypic and genotypic features of POC1B-associated cone dystrophy

ABSTRACT

Purpose

Patients with cone dystrophy (CD) can present with virtually normal retinal appearance, which may delay diagnosis. This study describes the inconspicuous clinical features of POC1B-associated CD in two Saudi families.

Methods

This is a retrospective case study. Clinical data analyzed included multimodal retinal imaging and electroretinography of the affected individuals. Genetic analysis was done for all probands.

Results

Three affected males from two Saudi families with POC1B-associated CD were included. The ages at presentation ranged from 18 to 34 years. Ophthalmic examination showed decreased Snellen visual acuities (range: 20/100–20/300) and color vision bilaterally. Fundus examination showed only mild vascular attenuation. Macular optical coherence tomography showed reduced reflectivity of the external limiting membrane, ellipsoid, and interdigitation zones. Full-field electroretinography demonstrated undetectable light-adapted responses and normal dark-adapted responses in all patients. Next-generation sequencing showed one proband to be homozygous for a previously unpublished nonsense variant in POC1B (NM_172240):c.672C>G; p(Tyr224*). Whole exome sequencing for the second proband showed a novel homozygous frameshifting variant in POC1B: c.991del; p(Arg331Glufs*13).

Conclusion

We described two novel variants in POC1B and the associated subtle, yet significant retinal features. POC1B-associated CD is a rare cause of visual loss in patients with relatively normal fundus appearance. Deep phenotyping is necessary in formulating appropriate differential diagnosis.

KEYWORDS:

• Cone dystrophy
• POC1B gene
• normal fundus appearance
• outer retinal atrophy
• inherited retinal disease

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

The author(s) reported that there is no funding associated with the work featured in this article.