Novel Bi-allelic PDE6C Variant Leads to Congenital Achromatopsia

Authors
Ata Bushehri 1
Davood Zare-Abdollahi 1
Hesam Hashemian 2
Ladan Safavizadeh 3
Jalil Effati 4
Hamid Reza Khorram Khorshid 1
1 Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
2 Department of Ophthalmology, Ophthalmology Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
3 Department of Opthomology, Ophthalmic Research Centre, Shahid Beheshti University (M.C.), Tehran, Iran
4 Meybod Genetic Research Center, Yazd, Iran
10.29252/ibj.24.4.257
Abstract
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