Molecular and clinical characterization of Thai patients with achromatopsia: identification of three novel disease-associated variants in theCNGA3andCNGB3genes

Purpose Achromatopsia (ACHM) is an autosomal recessive cone disorder characterized by pendular nystagmus, photophobia, reduced visual acuity, and partial or total absence of color vision. Mutations in six genes (CNGA3,CNGB3,GNAT2,PDE6C,PDE6H, andATF6) have been reported in ACHM. There is no information on these disease-associated genes in Thai population. This study aimed to investigate the molecular and clinical characteristics in Thai patients with ACHM. Methods Seven unrelated Thai patients with ACHM were recruited. Detailed ophthalmologic examination was performed. Polymerase chain reaction (PCR)-coupled single-strand conformation polymorphism (SSCP) screening followed by Sanger sequencing was used to identify sequence variants in all exons and splice junctions of three genes (CNGA3,CNGB3, andGNAT2). The pathogenicity of the detected variants was interpreted. Segregation analysis was performed to determine variant sharing in available family members. Results Four patients displayed different SSCP migration patterns. Sequence analysis revealed a reported pathogenic and a novel disease-associated variant in theCNGA3gene. For theCNGB3gene, we found two novel disease-associated variants and a reported variant of uncertain significance (VUS). Segregation analysis confirmed that the variants identified in each patient were present in the heterozygous state in their corresponding family members, which was consistent with an autosomal recessive mode of inheritance. Conclusions This study demonstrated the first molecular and clinical characterization of ACHM in Thai patients. The identification of disease-associated genes in a specific population leads to a personalized gene therapy benefiting those affected patients.