Novel variants in PDE6A and PDE6B genes and its phenotypes in patients with retinitis pigmentosa in Chinese families

Abstract

Background Retinitis pigmentosa (RP) is a genetically heterogeneous disease with 89 causative genes identified to date. However, only approximately 60% of RP cases genetically solved to date, predicating that many novel disease-causing variants are yet to be identified. The purpose of this study is to identify novel variants in PDE6A and PDE6B genes and present its phenotypes in patients with retinitis pigmentosa in Chinese families. Methods Five retinitis pigmentosa patients with PDE6A variants and three with PDE6B variants were identified through a hereditary eye disease enrichment panel (HEDEP), all patients’ medical and ophthalmic histories were collected, and ophthalmological examinations were performed, followed by an analysis of the possible causative variants. Sanger sequencing was used to verify the variants. Results We identified 20 variants in eight patients: 16 of them were identified in either PDE6A or PDE6B in a compound heterozygous state. Additional four heterozygous variants were identified in the genes ADGRA3, CA4, OPTN, RHO. Two novel genetic changes in PDE6A were identified (c.1246G > A and c.1747 T > A), three novel genetic changes in PDE6B were identified (c.401 T > C, c.2293G > C and c.1610-1612del), out of the novel identified variants one was most probably non-pathogenic (c.2293G > C), all other novel variants are pathogenic. Additional variant was identified in CA4 and RHO, which can cause ADRP (c.243G > A, c.688G > A). In addition, a novel variant in ADGRA3 was identified (c.921-1G > A). Conclusions This study reveals novel and known variants in PDE6A and PDE6B genes in Chinese families with autosomal recessive RP, and expands the clinical and genetic findings of photoreceptor-specific enzyme deficiencies.

PCYT1A deficiency disturbs fatty acid metabolism and induces ferroptosis in the mouse retina

“…IRDs are among the most complicated inherited diseases and show substantial genetic and clinical heterogeneity. Therefore, the pathogenic mechanisms involved are extraordinarily complex, and abnormalities in the phototransduction cascade [ 21 , 38 , 39 ], vitamin A metabolism [ 40 , 41 ], the cytoskeleton [ 42 ], cell adhesion [ 43 ], RNA splicing [ 44 ], and protein trafficking are the main known causes of the development of IRDs [ 45 ]. Generating appropriate animal models and determining the underlying pathogenic mechanisms are essential to understanding the pathogenesis of this disease.…”

PCYT1A deficiency disturbs fatty acid metabolism and induces ferroptosis in mice retina

“…Therefore, the pathogenic mechanisms of which are extraordinarily complex, and abnormalities in phototransduction cascade 20,33,34 , vitamin A metabolism 35,36 , cytoskeleton 37 , cell adhesion 38 , RNA splicing 39 , and proteins tra cking are the main known causes for the development of IRDs 40 .…”

Changes in Cyclic Guanosine Monophosphate Channel of 661w Cells In vitro with Excessive Light Time

“…In addition, the level of PDE6 was always expressed constantly because of the hydrolysis function of PDE6 induced by light. [ 23 , 30 ] However, the expression of GCAP1 and cGMP did not increase after 60 min. After being exposed to light for four days, we proposed that the cGMP-gated channel could not maintain the ability to regulate light conditions after 60 min.…”