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Purpose: Autosomal dominant optic atrophy (DOA) is a major cause of visual impairment in young adults that is characterized by selective retinal ganglion cell loss. To define the prevalence and natural history of this optic nerve disorder, we performed a population-based epidemiologic and molecular study of presumed DOA cases in the north of England., Design: Case series., Participants: Seventy-six affected probands with a clinical diagnosis of DOA were identified from our neuro-ophthalmology and neurogenetics database., Methods: OPA1 genetic testing was performed using a polymerase chain reaction-based sequencing strategy. OPA1-negative cases were then screened for large-scale OPA1 rearrangements and OPA3 mutations. Additional affected family members identified through contact tracing were examined, and longitudinal visual data were analyzed., Main Outcome Measures: The prevalence and molecular characteristics of DOA in the north of England. Visual function and disease progression among patients with OPA1-positive mutations., Results: The detection rate of OPA1 mutations was 57.6% among probands with a positive family history of optic atrophy (19/33) and 14.0% among singleton cases (6/43). Approximately two thirds of our families with DOA harbored OPA1 mutations (14/22, 63.6%), and 5 novel OPA1 mutations were identified. Only 1 family carried a large-scale OPA1 rearrangement, and no OPA3 mutations were found in our optic atrophy cohort. The minimum point prevalence of DOA in the north of England was 2.87 per 100,000 (95% confidence interval [CI], 2.54-3.20), or 2.09 per 100,000 (95% CI, 1.95-2.23) when only OPA1-positive cases were considered. Snellen visual acuity varied markedly between OPA1-positive cases with a mean of 20/173 (range 20/20 to hand movements), and visual function worsened in 67.4% of patients during follow-up. The mean rate of visual loss was 0.032 logarithm of the minimum angle of resolution per year, but some patients experienced faster visual decline (range = 0-0.171 logarithm of the minimum angle of resolution/year). OPA1 missense mutations were associated with a significantly worse visual outcome compared with other mutational subtypes (P=0.0001)., Conclusions: Dominant optic atrophy causes significant visual morbidity and affects at least 1 in 35,000 of the general population., (Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

The Drosophila esc gene is a Polycomb Group (PcG) gene whose product is essential for histone H3 K27 methylation and PcG silencing yet genetic analysis indicated that its product was needed only in the very early embryo. We know now that escl, a close homologue of esc exists in the Drosophila genome. In contrast with earlier studies, we find that both esc and escl are expressed at all stages of development. We show that three major differences between the two genes are in the transcriptional control, which allows esc to make a much stronger maternal contribution; in the splicing efficiency, which makes a major difference in the early escl function; and in the lower participation of ESCL in the PRC2 complex and lower enzymatic activity of the resulting complex. Both genes can sustain normal development in the absence of the other except for the critical role provided by maternal esc product in early embryonic development. Finally, using zygotic mutations in both genes, we show that the gradual loss of function of PRC2 activity leads first to a loss of histone H3 K27 methylation and only at a later stage to a gradual loss of PRC1 binding to chromatin.