Severe retinitis pigmentosa mapped to 4p15 and associated with a novel mutation in the PROM1 gene

Zhang, Qingjiong; Zulfiqar, Fareeha; Xiao, Xueshan; Ahmad, Zahoor; Caruso, Raphael; MacDonald, Ian M.; Sieving, Paul A.; Riazuddin, Sheikh; Hejtmancik, J. Fielding

doi:10.1007/s00439-007-0395-2

Cited by 90 publications

(70 citation statements)

References 26 publications

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“…17,41 The heterozygous mutation studied here results in a stable protein 7 and is perhaps insufficient to completely inhibit its function in the brain. In contrast, recessive mutations arise from either frameshift or nonsense mutations 5,6 that result in the generation of a premature stop codon and truncated protein. 5,6,42 In these cases, the homozygous patients display a severe eye phenotype, and polydactyly was also reported in one of the carriers, an additional symptom that confirms the existence of variable penetrance associated with PROM1.…”

Section: Discussionmentioning

confidence: 99%

“…5,18 From kindred A, the proband (A-V:1), her mother (A-IV:2), aunt (A-IV:4) and grandmother (A-III:6) were studied. In kindred B, the proband (B-II:1) and her mother (B-I:1) were included in the study (Table 1).…”

Section: Methodsmentioning

confidence: 99%

“…5,18 A-V:1 had steroid-resistant asthma. She had a clinical assessment for microscopic haematuria, with a normal renal ultrasound and intravenous pyelogram.…”

Section: Clinical Findingsmentioning

confidence: 99%

“…Using this paradigm, we have demonstrated roles for the genes PAX6, PITX2, SOX2, OTX2 and RIMS1 in human brain development and cognitive function. [1][2][3][4] Mutations in PROM1 have been shown to result in retinitis pigmentosa, 5,6 macular degeneration 7,8 and cone-rod dystrophy. 9 PROM1 encodes prominin-1, a 5-transmembrane glycoprotein also known as CD133 and AC133.…”

Section: Introductionmentioning

confidence: 99%

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Extended extraocular phenotype of PROM1 mutation in kindreds with known autosomal dominant macular dystrophy

et al. 2010

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Mutations in prominin 1 (PROM1) have been shown to result in retinitis pigmentosa, macular degeneration and cone-rod dystrophy. Because of the putative role of PROM1 in hippocampal neurogenesis, we examined two kindreds with the same R373C PROM1 missense mutation using our established paradigm to study brain structure and function. As the protein encoded by PROM1, known as CD133, is used to identify stem/progenitor cells that can be found in peripheral blood and reflect endothelial reparatory mechanisms, other parameters were subsequently examined that included measures of vascular function, endothelial function and angiogenic capacity. We found that aspects of endothelial function assayed ex vivo were abnormal in patients with the R373C PROM1 mutation, with impaired adhesion capacity and higher levels of cellular damage. We also noted renal infections, haematuria and recurrent miscarriages possibly reflecting consequences of abnormal tubular modelling. Further studies are needed to confirm these findings.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…5,18 A-V:1 had steroid-resistant asthma. She had a clinical assessment for microscopic haematuria, with a normal renal ultrasound and intravenous pyelogram.…”

Section: Clinical Findingsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Extended extraocular phenotype of PROM1 mutation in kindreds with known autosomal dominant macular dystrophy

et al. 2010

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“…The disease onset and progression may vary significantly among patients, even within the same family. The patients frequently experience night blindness in the early phase of the disease, The molecular basis of human retinal and vitreoretinal diseases Collin et al, 2008; den Hollander et al, 1999; Dryja et al, 1995; Gal et al., 2000; Huang et al, 1995; Martinez-Mir et al, 1998;Maw et al, 1997;Maw et al, 2000;McLaughlin et al, 1993; Morimura et al, 1998;Nakazawa et al, 1998; Rivolta et al, 2000;Thompson et al, 2001;Tuson et al, 2004;Zangerl et al, 2006;Zhang et al, 2007b) or dominant (Abid et al, 2006; Bowne et al, 2002; Chakarova et al, 2002; Chakarova et al, 2007;Farrar et al, 1991;Freund et al, 1997;Friedman et al, 2009; Kajiwara et al, 1991; Kajiwara et al, 1994; Keen et al, 2002; Kennan et al, 2002;McKie et al, 2001; Rebello et al, 2004; Sato et al, 2005;Vithana et al, 2001;Wada et al, 2001;Zhang et al, 2007a;Zhao et al, 2009), as well as X-linked (Meindl et al, 1996; Roepman et al, 1996a; Roepman et al, 1996b; Schwahn et al, 1998).Interestingly, mutations in several genes can be either dominant or recessive (Bernal et al, 2008; Bessant et al, 1999; Coppieters et al, 2007;Davidson et al, 2009; Dryja et al, 1990; Morimura et al, 1999; Pierce et al, 1999;Sullivan et al, 1999). The splicing category will now be discussed in more detail.…”

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confidence: 99%

The molecular basis of human retinal and vitreoretinal diseases

Berger¹,

Kloeckener-Gruissem²,

Neidhardt³

2010

Progress in Retinal and Eye Research

490

443

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The molecular basis of human retinal and vitreoretinal diseases pathologies of other tissues (syndromic forms) or only affects the retina, retinal pigment epithelium and the vireous body (non-syndromic forms). In addition, the mode of inheritance was used as one characteristic feature of the different disease phenotypes in order to categorize them. Our aim was to provide a comprehensive overview about the molecular basis of retinal and vitreoretinal diseases and to discuss selected aspects in more detail. Non-syndromic retinal and vitreoretinal diseases Diseases of rod photoreceptor cells (stationary and progressive)Rod photoreceptors represent the vast majority of light sensitive cells in the human retina. There are approximately 20 times more rods than cones. These cells are spezialized for low light intensities and are responsible for visual perception under dim light conditions. The center of the human retina, which contains the macula and fovea centralis, is devoid of rod photoreceptor cells but the flanking areas have the highest rod content, which decreases almost lineary towards the retinal periphery.The two major classes of stationary and progressive retinal diseases in humans arerepresented by different forms of stationary night blindness and retinitis pigmentosa, respectively. Congenital stationary night blindness / stationary rod diseasesAs the name implies, congenital stationary night blindness (CSNB) is a nonprogressive visual impairment present at birth. However, it is also one of the first symptoms in progressive diseases, including retinitis pigmentosa (RP). Therefore, a differential diagnosis by genetic testing can provide helpful and important information to the affected individuals and families, in order to exclude or confirm the clinical diagnosis and to provide counselling. Bech-Hansen et al., 1998; Bech-Hansen et al., 2000;Dryja et al., 1993; Dryja et al., 1996; Dryja et al., 2005; Fuchs et al., 1995;Gal et al., 1994;Li et al., 2009; Pusch et al., 2000;Strom et al., 1998;Wycisk et al., 2006;Yamamoto et al., 1997;Zeitz et al., 2005;Zeitz et al., 2006 inheritance. The disease was found to be due to mutations in the alpha subunit of transducin (Dryja et al., 1996). The Schubert Bornschein disease can be subdivided in (i) CSNB1 or complete CSNB and (ii) CSNB2 or incomplete CSNB. In CSNB1, the rod b-wave is significantly reduced or absent, while that of the cones is largely Retinitis pigmentosa and progressive rod cone diseasesThe term retinitis pigmentosa (RP) describes a group of clinically similar phenotypes associated with genetically heterogeneous causes. The disease onset and progression may vary significantly among patients, even within the same family. The patients frequently experience night blindness in the early phase of the disease, The molecular basis of human retinal and vitreoretinal diseases Collin et al., 2008; den Hollander et al., 1999; Dryja et al., 1995; Gal et al., 2000; Huang et al., 1995; Martinez-Mir et al., 1998;Maw et al., 1997;Maw et al., 2000;McLaughlin et a...

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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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Severe retinitis pigmentosa mapped to 4p15 and associated with a novel mutation in the PROM1 gene

Cited by 90 publications

References 26 publications

Extended extraocular phenotype of PROM1 mutation in kindreds with known autosomal dominant macular dystrophy

Extended extraocular phenotype of PROM1 mutation in kindreds with known autosomal dominant macular dystrophy

The molecular basis of human retinal and vitreoretinal diseases

Clinical and Molecular Characterization ofPROM1-Related Retinal Degeneration

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