Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Department of Ophthalmology, Ophthalmology Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Iran Biomed J. 2020 Jul;24(4):257-63. doi: 10.29252/ibj.24.4.257. Epub 2020 Dec 28.
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.
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.
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.
Our data extended the phenotypic spectrum of retinal disorders caused by PDE6C variants and provided new clinical and genetic information on achromatopsia.
携带磷酸二酯酶 6C（PDE6C）变异的色盲症患者的临床表型在文献中描述甚少。PDE6C 编码锥状磷酸二酯酶的催化亚基，该酶水解环状鸟苷单磷酸，作为光转导级联的最后一步，使光感受器细胞膜超极化。
在本研究中，来自一个近亲家庭的两名患者接受了全面的眼科检查和分子研究，包括 WES。使用计算机分子建模分析了该变异对蛋白质功能的影响。
患者被鉴定为色盲症，携带位于 10q23 染色体上的 PDE6C 基因的纯合错义变异（c.C1775A:p.A592D）。分子建模表明，该变异会导致蛋白质构象改变，并导致磷酸二酯酶活性降低。
我们的数据扩展了由 PDE6C 变异引起的视网膜疾病的表型谱，并为色盲症提供了新的临床和遗传信息。
