Novel PDE6B Mutation Presenting with Retinitis Pigmentosa – A Case Series of Three Patients

Abstract

Background Retinitis pigmentosa (RP) affects 2.5 million people worldwide. Increased identification of causative gene defects and the increasing possibility of treatment necessitates better knowledge of phenotype-genotype correlations to help identify patients who would benefit from targeted gene therapy and improve patientsʼ care. Here, we report on three RP patients with mutations in the PDE6Β Gene that have not been described previously. History and Signs Three patients with a PDE6Β mutation were identified: 1. A 30-year-old male with a homozygotous mutation (c.[2351dupA],[2351dupA], p.[Q785Gfs*20],[Q785Gfs*20]) who was followed for 8 years. 2. A 54-year-old Caucasian woman with a heterozygous mutation [p.(K611Nfs*6), p.(Q567*)] who was followed for 40 years. 3. A 46-year-old Caucasian male [p.(E271K), p.(R627_E631del)]. All had noted an onset in childhood and complained of night blindness and photophobia. Typical bone spiculae were seen, and peripheral visual fields were progressively affected in all patients. Ganzfeld-ERG showed typical signs of rod-cone dystrophy. Patients 1 and 2 underwent cataract surgery at ages 27 and 36 years with an improvement in vision, while patient 3 had not developed a cataract at age 54. Conclusions In children complaining of night blindness, a PDE6Β-associated RP needs to be taken into consideration. Apart from helping patients with optical aids, such as polarizing filters or magnification, a specific diagnosis is especially important in view of emerging genetic treatment options. In particular, in RP patients with a PDE6Β mutation, a phase I/II study is currently ongoing (https://clinicaltrials.gov/ct2/show/NCT03328130).

PDE6C: Novel Mutations, Atypical Phenotype, and Differences Among Children and Adults

“… 4 Rods have a PDE6 catalytic core composed of a heterodimer of PDE6A and PDE6B subunits (inhibited by PDE6G), whereas cones have a catalytic homodimer of PDE6C (inhibited by PDE6H subunits). 5 This explains why mutations in PDE6A (OMIM #180071), PDE6B (OMIM #180072) and PDE6G (OMIM #180073) cause autosomal recessive retinitis pigmentosa and autosomal dominant congenital stationary night blindness (both rod-related diseases), 6 , 7 whereas homozygous or compound heterozygous mutations in PDE6C and PDE6H (OMIM #600827 and #601190) lead to predominantly cone dysfunction disorders, such as achromatopsia (ACHM) and autosomal recessive cone dystrophy. 8 , 9 …”

Gene therapy in hereditary retinal dystrophy

“…The clinical trial PRE65 gene viral gene therapy in retinal dystrophy was approved by the first Food and Drug Administration (FDA)[ 16 ]. Afterward, many specified genes associated with HRD were delivered for treating RP[ 17 18 19 ], Bietti's crystalline dystrophy (NCT No. 04722107), choroideremia[ 20 21 ], LCA[ 22 ], X-linked retinoschisis[ 23 ], and Stargardt diseases[ 20 ] in clinical trials.…”

Treatment Of Hereditary Retinal Dystrophies. Perspectives And Social Aspects

“…Понастоящем се провеждат множество клинични проучвания за лечение на голяма част от НДР, при които се използват възможностите на генната терапия, аденовирусни вектори, заместващи дефектния ген, се поставят субретинално [9][10][11][12][13][14].…”