Genetic identification and molecular modeling characterization reveal a novel<i>PROM1</i>mutation in Stargardt4-like macular dystrophy

Imani, Saber; Cheng, Jingliang; Shasaltaneh, Marzieh Dehghan; Wei, Chunli; Yang, Lisha; Fu, Shangyi; Zou, Hui; Zhang, Xianqin; Chen, Hanchun; Zhang, Dianzheng; Duan, Chengxia; Lv, Hongbin; Li, Yumei; Chen, Rui; Fu, Junjiang

doi:10.18632/oncotarget.22343

Cited by 40 publications

(24 citation statements)

References 69 publications

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“…However, there are other clinically overlapping phenotypes, inherited both in autosomal dominant (ad) and recessive manner. Mutations in ELOVL4 and PROM1 lead to adSTGD-like phenotype and are known as STGD3 (MIM# 600 110) and STGD4 (MIM# 603786), respectively [7]. Similarly, heterozygous mutations in PRPH2, BEST1 and CRX, and bi-al-lelic variants in CRB1, RAB28, RDH11 and ROM1 are also known to cause STGD-like phenotypes [8 -13].…”

Section: Stgd-like Phenotypes Due To Variants In Other Genesmentioning

confidence: 99%

ABCA4-Associated Stargardt Disease

Khan

Cremers

2020

Klin Monatsbl Augenheilkd

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Autosomal recessive Stargardt disease (STGD1) is associated with variants in the ABCA4 gene. The phenotypes range from early-onset STGD1, that clinically resembles severe cone-rod dystrophy, to intermediate STGD1 and late-onset STGD1. These different phenotypes can be correlated with different combinations of ABCA4 variants which can be classified according to their degree of severity. A significant fraction of STGD1 cases, particularly late-onset STGD1 cases, were shown to carry only a single ABCA4 variant. A frequent coding variant (p.Asn1868Ile) was recently identified which – in combination with a severe ABCA4 variant – is generally associated with late-onset STGD1. In addition, an increasing number of rare deep-intronic variants have been found and some of these are also associated with late-onset STGD1. The effect of these and other variants on ABCA4 RNA was tested using in vitro assays in human kidney cells using specially designed midigenes. With stem cells and photoreceptor progenitor cells derived from patient skin or blood cells, retina-specific splice defects can be assessed. With expert clinical examination to distinguish STGD1 cases from other maculopathies, as well as in-depth genomics and transcriptomics data, it is now possible to identify both mutant ABCA4 alleles in > 95% of cases.

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Section: Stgd-like Phenotypes Due To Variants In Other Genesmentioning

confidence: 99%

ABCA4-Associated Stargardt Disease

Khan

Cremers

2020

Klin Monatsbl Augenheilkd

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“…Prominin 1 ( PROM1 ; OMIM 604365 ) is commonly associated with cone-rod dystrophies. 1 However, throughout the literature, variations in PROM1 have been implicated in extremely varied and overlapping phenotypes that have been described as retinitis pigmentosa 2 , 3 , 4 , 5 , 6 , 7 , 8 ; retinitis pigmentosa with macular involvement 9 ; retinal dystrophy 8 ; cone-rod dystrophy 1 , 8 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ; bull’s-eye maculopathy 18 ; bull’s-eye maculopathy associated with rod, rod-cone, and macular dystrophy 19 ; Stargardt-like disease 20 , 21 , 22 , 23 ; macular dystrophy 24 ; and maculopathy with rod-cone dystrophy. 25 The age at onset, presenting symptoms, and severity of disease vary with sequence variations.…”

Section: Introductionmentioning

confidence: 99%

Clinical and Molecular Characterization ofPROM1-Related Retinal Degeneration

et al. 2019

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Key Points Question What are the clinical and molecular characteristics of PROM1- related retinal degeneration? Findings In this case series of 19 patients with PROM1 -related retinal degeneration, recessive variants were associated with early-onset, severe panretinal degeneration, whereas the dominant disease was associated with the c.1117C>T variant and a late-onset, milder phenotype that predominantly involves the macula. In addition, the dominant variant was preferentially associated with cone photoreceptors. Meaning A better understanding of the clinical and molecular characteristics of PROM1- related retinal degeneration may aid development of future treatments, including gene therapy and optogenetics.

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“…Missense and truncating mutations predominantly occurred within protein-coding sequences. Mutations in PROM1 were mainly missense and truncating mutations, including p.R373C, p.Y452fsX12, p. G614fsX626, and p.Q576X in the prominin domain, which are associated with human inherited diseases [95][96][97][98]. A recent study reported the identification of a point mutation at p.S281R (serine [S] changed to arginine [R] due the mutation of thymine [T] to guanine [G]) in the prominin domain of the PROM1 protein in 8/555 lung cancer patients [99].…”

Section: Discussionmentioning

confidence: 99%

PROM1 and PROM2 expression differentially modulates clinical prognosis of cancer: a multiomics analysis

et al. 2019

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Prominin 1 (PROM1) is considered a biomarker for cancer stem cells, although its biological role is unclear. Prominin 2 (PROM2) has also been associated with certain cancers. However, the prognostic value of PROM1 and PROM2 in cancer is controversial. Here, we performed a systematic data analysis to examine whether prominins can function as prognostic markers in human cancers. The expression of prominins was assessed and their prognostic value in human cancers was determined using univariate and multivariate survival analyses, via various online platforms. We selected a group of prominent functional protein partners of prominins by protein-protein interaction analysis. Subsequently, we investigated the relationship between mutations and copy number alterations in prominin genes and various types of cancers. Furthermore, we identified genes that correlated with PROM1 and PROM2 in certain cancers, based on their levels of expression. Gene ontology and pathway analyses were performed to assess the effect of these correlated genes on various cancers. We observed that PROM1 was frequently overexpressed in esophageal, liver, and ovarian cancers and its expression was negatively associated with prognosis, whereas PROM2 overexpression was associated with poor overall survival in lung and ovarian cancers. Based on the varying characteristics of prominins, we conclude that PROM1 and PROM2 expression differentially modulates the clinical outcomes of cancers.

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Genetic identification and molecular modeling characterization reveal a novelPROM1mutation in Stargardt4-like macular dystrophy

Cited by 40 publications

References 69 publications

ABCA4-Associated Stargardt Disease

ABCA4-Associated Stargardt Disease

Clinical and Molecular Characterization ofPROM1-Related Retinal Degeneration

PROM1 and PROM2 expression differentially modulates clinical prognosis of cancer: a multiomics analysis

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