The genetic spectrum of achromatopsia in consanguineous families: insights from Whole exome sequencing across 15 affected individuals

INTRODUCTION: ) are known to be the primary causes of ACHM, affecting the normal function of the cone photoreceptors. METHODOLOGY: Whole-exome sequencing was performed in five families with 15 affected individuals. Candidate variants, prioritized using VARDIGS, were confirmed by Sanger sequencing and evaluated according to ACMG (2015) criteria. In-silico protein modeling and molecular dynamics simulations were employed to predict structural consequences of the variants. RESULTS: : c.1336 G > T p.(Glu446Ter), all consistent with cone dystrophies phenotypes. CONCLUSION: Our findings expand the mutational spectrum of achromatopsia and other inherited retinal diseases. To the best of our knowledge, these variants have been reported for the first time in Pakhtun ethnic group of Pakistani population. The identification of pathogenic variants provides valuable insight for future research on gene therapy eligibility and personalized medicine.