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D.G. Birch, D.H. Wheaton, K.G. Locke, S.J. Bowne, L.S. Sullivan, S.P. Daiger; Clinical Characterization of RP11 in Five Families With Identified PRPF31 Mutations . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1037.
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Mutations in the pre–mRNA splicing gene PRPF31 cause RP11, a form of autosomal dominant RP characterized by non–penetrance in some obligate carriers. The variations in expression of wild type PRPF31 which are suspected of causing non–penetrance might also be expected to produce large variations in disease severity among affected individuals. We therefore characterized visual function in members from five affected pedigrees.
Affected (n=14; 9–65 yrs) and unaffected individuals (n=6; 5–62 yrs) from five families volunteered for the study. In addition to a routine ophthalmologic examination, visual function assessment included visual acuity, static perimetric thresholds, rod absolute thresholds, full–field electroretinography, and fundus photography.
Four families had termination or missense mutations in PRPF31. Patients in these families were diagnosed at an early age and experienced early peripheral field loss. Rod ERG responses were non–detectable in all (n=12) including children as young as age 9 yrs. Cone responses were typically in the sub–microvolt range with delayed implicit time. Nevertheless, macula function (visual acuity, cone perimetric thresholds and rod absolute thresholds) was relatively well preserved. Even in families with reduced penetrance (i.e., completely normal results on all tests in an unaffected 62–year–old obligate carrier), there was little variability in phenotype among the affected family members. In a fifth family with a splice–site mutation, there was greater variability with one individual retaining a 33 µV cone ERG and measurable rod ERG function into adulthood.
Despite variations in age and mutation among these patients, a fairly consistent phenotype emerged. Most patients showed early field and ERG loss with relative preservation of central retinal function. This uniformity of phenotype is not consistent with the range of severity expected due to continuous variation in expression of the wild–type allele, but is consistent with a dichotomous trait or a threshold model.
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