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Ditta Zobor, Steffen Link, Nicole Weisschuh, Gergely Zobor, Susanne Kohl, Bernd Wissinger, Eberhart Zrenner; Genotype-phenotype Analysis In Patients With Autosomal Recessive Retinitis Pigmentosa (arRP) Due To PDE6A Mutations. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4564.
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To investigate disease characteristics and perform genotype-phenotype correlations in patients with arRP due to mutations in the gene encoding the α-subunit of the rod cGMP-phosphodiesterase 6 (PDE6A).
Eight patients (3 female, 5 male; 2 sibling pairs; mean age: 38.25, range: 18 to 44 years) with known mutations in the PDE6A gene were examined. Besides psychophysical tests (visual acuity, visual field, color vision, dark adaptation) a detailed electrophysiological examination was performed including Ganzfeld and multifocal ERG (mfERG). Furthermore, fundus photography, autofluorescence imaging and spectral domain OCT imaging was carried out for an in-depth morphological characterization.
Molecular genetic testing in patients affected by arRP identified eight patients carrying mutations in PDE6A - five of which were homozygous. One sib pair was homozygous for the p.Val685Met mutation, the other sib pair for the p.Arg102Ser mutation and one patient was homozygous for the p.Arg257X mutation. The remaining three patients carried compound heterozygous mutations: p.Val685Met in combination with either p.Arg102Ser, p.Arg562Trp, or p.Leu621Arg, respectively. The siblings homozygous for p.Val685Met showed a markedly reduced visual acuity (mean VA: 0.05), small residual visual fields (mean VF for target III4e: 187.5 deg2) and no recordable ERG responses. In comparison, the compound-heterozygotes revealed a significantly better visual function (mean VA: 0.8; mean VF: 1251 deg2). Although Ganzfeld ERGs were - with one exception - extinguished in the compound-heterozygous patients as well, mfERG could detect residual responses in every case (mean central response amplitude: 21.6 nV/deg2) with normal implicit times (mean IT: 29.1 ms). The patients homozygous for p.Arg102Ser presented with well-preserved visual function (mean VA: 1.0, mean VF: 10936.1 deg2) and recordable electrophysiological responses. Fundus morphology revealed typical changes of RP in all patients, the central retinal thickness (CRT) observed in OCT imaging corresponded well with the remaining visual function (mean CRT in the p.Val685Met homozygous sibs: 97.75 μm; mean CRT in the compound-heterozygotes: 215.25 μm; and 220 μm in the Arg102Ser homozygotes). The patient homozygous for p.Arg257X was the youngest with a well-preserved visual function and central retinal morphology.
All patients with PDE6A mutations presented with typical features of RP, however, depending on the genotype, severity of disease varied considerably. In these patients, the Val685Met mutation seemed to cause worse clinical outcome, especially if patients were homozygous for this mutation.
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