The genetic basis of clinically-suspected achromatopsia in the United Arab Emirates.

Abstract

Purpose: Achromatopsia (ACHM) is a genetically heterogenous relatively stationary congenital autosomal recessive cone disorder characterized typically by photophobia, low vision, nystagmus, hyperopia, grossly normal retinal appearance, and absent photopic responses by full-field electroretinography. Incomplete forms occur as well. This study investigates the genetic basis of clinically-suspected ACHM in the United Arab Emirates.

Methods: Retrospective case series (January 2016-December 2023) of patients with (1) clinically-suspected ACHM and (2) mutations in ACHM-associated genes (CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, AT6).

Results: Twenty-two clinically-suspected patients (19 probands) were identified. Biallelic disease genes and number of probands were CNGA3 (9), CNGB3 (6), PDE6C (1), GNAT2 (1), RGS9BP (1), and CNNM4 (1). Two probands had their diagnoses revised after genetic testing and phenotypic reassessment to RGS9BP-related bradyopsia and CNNM4-related Jalili syndrome. Three additional cases (making 22 total probands) were identified from ACHM gene mutation review - one each related to PDE6C, to AT6, and to CNGB3 in concert with CNGA3 (triallelic disease). All three presented with macular discoloration, an atypical finding for classic ACHM.

Conclusion: CNGA3 was the single most frequent implicated gene. Bradyopsia and Jalili syndrome can resemble incomplete ACHM. Macular discoloration on presentation can occur in PDE6C-related disease, AT6-related disease, and triallelic CNGB3/CNGA3-related disease. The possibility for triallelic disease exists and requires genetic counseling beyond that of simple autosomal recessive inheritance.