Identification of the PROM1 Mutation p.R373C in a Korean Patient With Autosomal Dominant Stargardt-like Macular Dystrophy

Abstract

Stargardt-like macular dystrophy 4 (STGD4) is a rare macular dystrophy characterized by bull's eye atrophy of the macula and the underlying retinal pigment epithelium. Patients with STGD4 show decreased central vision, which often progresses to severe vision loss. The PROM1 gene encodes prominin-1, which is a 5-transmembrane glycoprotein also known as CD133 and is involved in photoreceptor disk morphogenesis. PROM1 mutations have been identified as genetic causes for STGD4 and other retinal degenerations such as retinitis pigmentosa. We report a case of STGD4 with a PROM1 p.R373C mutation in a Korean patient. Ophthalmic examinations of a 38-yr old man complaining of decreased visual acuity revealed bilateral atrophic macular lesions consistent with STGD4. Targeted exome sequencing of known inherited retinal degeneration genes revealed a heterozygous missense mutation c.1117C>T (p.R373C) of PROM1, which was confirmed by Sanger sequencing. To the best of our knowledge, this is the first case of a PROM1 mutation causing STGD4 in Koreans.

Clinical and genetic characteristics of 10 Japanese patients with PROM1‐associated retinal disorder: A report of the phenotype spectrum and a literature review in the Japanese population

“…In our cohort, all 10 affected subjects showed concentrated macular atrophy in fundus photographs, and the atrophic or mottled areas were clearly demonstrated on FAF images. The very similar macular findings on fundus and FAF images found in our cohort were identified in previous studies of a specific variant (p.Arg373Cys) (Cehajic-Kapetanovic et al, 2019;Kim et al, 2017;Michaelides et al, 2010). It is of note, however, the peripheral atrophic changes were also found in a previous study (Michaelides et al, 2010).…”

“…Variants in the PROM1 gene have been associated with CORD/COD, MD, STGD, and RP (Arai et al, 2015; Arrigoni et al, 2011; Beryozkin et al, 2014; Birtel et al, 2018; Boulanger‐Scemama et al, 2015; Carss et al, 2017; Cehajic‐Kapetanovic et al, 2019; Collison et al, 2019; Eidinger et al, 2015; Eisenberger et al, 2013; Imani et al, 2018; Jinda et al, 2014; Khan & Bolz, 2015; Kim et al, 2017, 2019; Kniazeva et al, 1999; Liang et al, 2019; Littink et al, 2010; Liu et al, 2016; Maw et al, 2000; Mayer et al, 2016; Michaelides et al, 2005, 2010; Michaelides, Johnson, et al, 2003; Permanyer et al, 2010; Pras et al, 2009; Ragi et al, 2019; Salles et al, 2017; Song et al, 2011; Strauss et al, 2018; Wawrocka et al, 2018; Yang et al, 2008; Zhang et al, 2007; Zhao et al, 2015). Over 90 disease‐associated PROM1 variants have been identified in AD and AR manners (The Human Gene Mutation Database; http://www.hgmd.cf.ac.uk/ac/index.php) (Supporting Information 1).…”

Characterization of PROM1 p.Arg373Cys Variant in a Cohort of Chinese Patients: Macular Dystrophy Plus Peripheral Bone-Spicule Degeneration

“…The characteristics of the fundus changes observed in the current study may be of help in explaining the various forms of retinal degeneration associated with the p.Arg373Cys variant, such as Stargardt-like macular dystrophy with yellowish flecks, 3,9 specific bull's eye retinal pigment epithelium dystrophy with central fovea sparing, 3,11,14 and occasionally severe macular dystrophy accompanied by possible pigmentation changes in the peripheral retina. 11,16 Characteristic macular involvement was found in all previously reported patients of 28 families with the p.Arg373Cys variant, 3,[9][10][11][12][13][14][15][16]19,28 which might overlap with cone-rod dystrophy and progression to rod-cone like dystrophy over time. 29 In addition, severe macular dystrophy, bull's eye fundus changes, and cone-rod dystrophy associated with the p.Arg373Cys variant may actually be present in the same eye, between two eyes of the same patient, or among different affected individuals in the same family if they are examined by different methods (with or without ERG or FFA) at different times or by different people.…”

Identification of a PROM1 mutation in a Spanish family with inherited retinal dystrophies

“…Mutations in PROM1 associated with hereditary retinal diseases have been previously described. The most recent case described in the literature of this mutation was reported by Kim et al in a Korean patient with Stargardt-like dystrophy [7]. Moreover, Michaelides et al identified the related chromosomal locus in 11 members of a five-generation British family with a dominantly inherited macular dystrophy [8].…”