Background: The clinical phenotyping of patients with achromatopsia harboring variants in phosphordiesterase 6C (PDE6C) has poorly been described in the literature. PDE6C encodes the catalytic subunit of the cone phosphodiesterase, which hydrolyzes the cyclic guanosine monophosphate that proceeds with the hyperpolarization of photoreceptor cell membranes, as the final step of the phototransduction cascade.
Methods: In the current study, two patients from a consanguineous family underwent full ophthalmologic examination and molecular investigations including WES. The impact of the variant on the functionality of the protein has been analyzed using in silico molecular modeling.
Results: The patients identified with achromatopsia segregated a homozygous missense variant (c.C1775A:p.A592D) in PDE6C gene located on chromosome 10q23. Molecular modeling demonstrated that the variant would cause a protein conformational change and result in reduced phosphodiesterase activity.
Conclusion: Our data extended the phenotypic spectrum of retinal disorders caused by PDE6C variants and provided new clinical and genetic information on achromatopsia.
Keywords: Achromatopsia; PDE6C; Whole exome sequencing.