North Carolina Macular Dystrophy: Phenotypic Variability and Computational Analysis of Disease-Associated Noncoding Variants

Purpose North Carolina macular dystrophy (NCMD) is an autosomal dominant, congenital disorder affecting the central retina. Here, we report clinical and genetic findings in three families segregating NCMD use epigenomic datasets from human tissues to gain insights into effect of NCMD-implicated variants. Methods Clinical assessment testing were performed. Publicly available transcriptomic analyzed activity-by-contact method for scoring enhancer elements linking them target genes was used. Results A previously described, heterozygous, noncoding variant upstream PRDM13 gene detected all six affected study participants (chr6:100,040,987G>C [GRCh37/hg19]). Interfamilial intrafamilial variability observed; visual acuity ranged 0.0 1.6 LogMAR fundoscopic visually insignificant, confluent, drusen-like deposits coloboma-like lesions. Variable degrees peripheral retinal spots (which easily on widefield imaging) observed subjects. Notably, a 6-year-old patient developed choroidal neovascularization required treatment with intravitreal bevacizumab injections. Computational analysis five single nucleotide variants that have been implicated revealed these changes lie within two putative elements; are predicted interact developing found be expressed fetal retina, greatest expression amacrine precursor cell population. Conclusions We provide further evidence supporting role dysregulation pathogenesis highlight usefulness imaging individuals suspected this condition.