Novel Variants in Phosphodiesterase 6A and Phosphodiesterase 6B Genes and Its Phenotypes in Patients With Retinitis Pigmentosa in Chinese Families

Abstract

Background: Retinitis pigmentosa (RP) is a genetically heterogeneous disease with 65 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 phosphodiesterase 6A and phosphodiesterase 6B 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, then we analysed the possible causative variants. Sanger sequencing was used to verify the variants.Results: We identified 20 mutations sites in eight patients, two heterozygous variants were identified per patient of either PDE6A or PDE6B variants, others are from CA4, OPTN, RHO, ADGRA3 variants. We identified two novel variants in PDE6A: c.1246G > A;p.(Asp416Asn) and c.1747T > A;p.(Tyr583Asn). Three novel mutations in PDE6B: c.401T > C;p.(Leu134Pro), c.2293G > C;p.(Ala765Pro) and c.1610-1612del;p.(537-538del).CA4: c.243G > A;p.(Trp81*) and RHO: c.688G>A;p.(Val230Ile) are novel variants and maybe affecting the phenotype. Among them, c.401T > C;p.(Leu134Pro) variant in PDE6B is non- pathogenic; RHO: c.688G>A;p.(Val230Ile) is conflicting interpretations of pathogenicity;Other novel variants are all pathogenic.Conclusions: This study reveals novel and known variants in Chinese families with PDE6A and PDE6B mutations in autosomal recessive RP, expanding the clinical and genetic findings of photoreceptor-specific enzyme deficiencies.