Michaelides et al. (2003) described a nonconsanguineous British family in which 11 members in 5 generations had a 'bull's eye' macular dystrophy first evident in the first or second decade of life. All of those affected had mild ... Michaelides et al. (2003) described a nonconsanguineous British family in which 11 members in 5 generations had a 'bull's eye' macular dystrophy first evident in the first or second decade of life. All of those affected had mild visual impairment and central scotomata. Electrophysiologic testing indicated that most individuals had disease confined to the central retina, but older subjects had more widespread rod and cone abnormalities, as demonstrated by flash electroretinogram. Michaelides et al. (2010) examined affected members of 3 families known to carry the R373C mutation in the PROM1 gene (604365.0003), including a Caribbean family with Stargardt disease-4 (STGD4; 603786), originally reported by Kniazeva et al. (1999), the British family with MCDR2, originally reported by Michaelides et al., 2003, and an Italian family with cone-rod dystrophy-12 (CORD12; 612657), originally reported by Yang et al. (2008), as well as 2 newly ascertained British families with MCDR2 (families 'D' and 'E'). The authors observed that in contrast to PROM1 mutations that cause a severe form of autosomal recessive retinitis pigmentosa (RP41; 612095), the R373C mutation produces an autosomal dominant, fully penetrant retinopathy characterized by the consistent finding of bull's eye maculopathy, with variable rod or rod-cone dysfunction displaying marked intra- and interfamilial variability, and phenotypes ranging from isolated maculopathy without generalized photoreceptor dysfunction to maculopathy associated with very severe rod-cone dysfunction. Michaelides et al. (2010) noted that all reported patients with the R373C mutation exhibited only an ocular phenotype, despite ubiquitous expression of PROM1 in plasma membrane protrusions. Arrigoni et al. (2011) reexamined affected members of 2 families with autosomal dominant macular degeneration and the R373C PROM1 mutation, i.e., the family reported by Michaelides et al. (2003) and family 'D' (Sisodiya, 2011) reported by Michaelides et al. (2010). Because of the putative role of PROM1 in hippocampal neurogenesis, Arrigoni et al. (2011) studied brain structure and function, and also examined other parameters including measures of vascular and endothelial function and angiogenic capacity. They found that 3 of the 4 members examined from 1 family had empty sella turcica on brain MRI, 2 of whom also had impaired olfaction; MRI was normal in the 2 patients examined from the second family, although 1 also had impaired olfaction. Aspects of endothelial function assayed ex vivo were abnormal in patients with the R373C mutation compared to controls, with impaired adhesion capacity and higher levels of cellular damage. Renal infections, hematuria, and recurrent miscarriages were also noted in these patients. Arrigoni et al. (2011) stated that further studies were needed to confirm these findings.
In affected members of a 5-generation British family with autosomal dominant 'bull's eye' macular dystrophy, previously reported by Michaelides et al. (2003), Yang et al. (2008) identified heterozygosity for a missense mutation in the PROM1 gene (604365.0003). Yang ... In affected members of a 5-generation British family with autosomal dominant 'bull's eye' macular dystrophy, previously reported by Michaelides et al. (2003), Yang et al. (2008) identified heterozygosity for a missense mutation in the PROM1 gene (604365.0003). Yang et al. (2008) identified the same mutation in a family with Stargardt disease-4 and in a family with cone-rod dystrophy (CORD12; 612657); the mutation was not found in 400 matched controls.