Mutations in PRDM5 in Brittle Cornea Syndrome Identify a Pathway Regulating Extracellular Matrix Development and Maintenance

Wright, Emma M.M. Burkitt; Spencer, Helen; Daly, Sarah B.; Manson, Forbes D.C.; Zeef, Leo; Urquhart, Jill; Zoppi, Nicoletta; Bonshek, Richard; Tosounidis, Ioannis; Mohan, Meyyammai; Madden, Colm; Dodds, Annabel; Chandler, Kate; Banka, Siddharth; Au, Leon; Clayton‐Smith, Jill; Khan, Naz; Biesecker, Leslie G.; Wilson, Meredith; Rohrbach, Marianne; Colombi, Marina; Giunta, Cecilia; Black, Graeme

doi:10.1016/j.ajhg.2011.07.013

Cited by 10 publications

(15 citation statements)

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“…Because not all BCS patients harbored ZNF469 mutations, a second locus for BCS was suspected. This was confirmed by the discovery of mutations in PRDM5 (MIM 614161) [Burkitt Wright et al, ]. PRDM5 encodes a C2H2 zinc finger protein of the PR/SET family of proteins.…”

Section: Brittle Cornea Syndrome (Bcs)mentioning

confidence: 94%

“…The following PRDM5 mutations have been reported: Three frameshift mutations: c.1517_1527del11, p.(Val506Glufs*5); c.974delG, p.(Cys325Leufs*2); and c.711_714delTGTT, p.(Val238Alafs*35), one nonsense mutation (c.1768C>T, p.(Arg590*)), two missense mutations (c.320A>G, p.(Tyr107Cys) and c.17T>G, p.(Val6Gly)), one splice site mutation (c.93+1G>A), and one multiple‐exon deletion (exons 9–14) [Burkitt Wright et al, ; Avgitidou et al, ].…”

Section: Brittle Cornea Syndrome (Bcs)mentioning

confidence: 99%

“…To provide a comprehensive overview of the clinical phenotype of BCS, we reviewed the data on 51 patients ( ZNF469 : n = 32; PRDM5: n = 19) (Table S1) [Al‐Hussain et al, ; Abu et al, ; Christensen et al, ; Khan et al, ; Burkitt Wright et al, ; Al‐Owain et al, ; Aldahmesh et al, ; Rohrbach et al, ; Ramappa et al, ; Avgitidou et al, ; Porter et al, ]. Only those patients with individual clinical and molecular data were included in the review.…”

Section: Brittle Cornea Syndrome (Bcs)mentioning

confidence: 99%

“…Heterozygous carriers may have very mild corneal thinning (e.g., CCT around 500 µm). Keratoconus has also been diagnosed in a young adult, heterozygous for a PRDM5 mutation [Burkitt Wright et al, ].…”

Section: Brittle Cornea Syndrome (Bcs)mentioning

confidence: 99%

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The Ehlers–Danlos syndromes, rare types

Brady¹,

Demirdas²,

Fournel‐Gigleux³

et al. 2017

American J of Med Genetics Pt C

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187

288

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The Ehlers–Danlos syndromes comprise a clinically and genetically heterogeneous group of heritable connective tissue disorders, which are characterized by joint hypermobility, skin hyperextensibility, and tissue friability. In the Villefranche Nosology, six subtypes were recognized: The classical, hypermobile, vascular, kyphoscoliotic, arthrochalasis, and dermatosparaxis subtypes of EDS. Except for the hypermobile subtype, defects had been identified in fibrillar collagens or in collagen‐modifying enzymes. Since 1997, a whole spectrum of novel, clinically overlapping, rare EDS‐variants have been delineated and genetic defects have been identified in an array of other extracellular matrix genes. Advances in molecular testing have made it possible to now identify the causative mutation for many patients presenting these phenotypes. The aim of this literature review is to summarize the current knowledge on the rare EDS subtypes and highlight areas for future research. © 2017 Wiley Periodicals, Inc.

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Section: Brittle Cornea Syndrome (Bcs)mentioning

confidence: 94%

Section: Brittle Cornea Syndrome (Bcs)mentioning

confidence: 99%

Section: Brittle Cornea Syndrome (Bcs)mentioning

confidence: 99%

Section: Brittle Cornea Syndrome (Bcs)mentioning

confidence: 99%

See 2 more Smart Citations

The Ehlers–Danlos syndromes, rare types

Brady¹,

Demirdas²,

Fournel‐Gigleux³

et al. 2017

American J of Med Genetics Pt C

Self Cite

187

288

View full text Add to dashboard Cite

show abstract

“…While a causal relationship is likely in some, for example in brittle cornea syndrome and other connective tissue disorders, other associations may be coincidental or due to reporting bias. Literature review is further complicated by possible diagnostic confusion between different types of Ehlers–Danlos syndrome and brittle cornea syndrome [Cameron, ; Burkitt Wright et al, ]. Recently identified linkage to LOX polymorphisms [Bykhovskaya et al, ] supports connective tissue weakness as a predisposing factor.…”

Section: Discussionmentioning

confidence: 99%

Keratoconus in Costello Syndrome

Gripp

Demmer

2013

American J of Med Genetics Pt A

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Keratoconus is a corneal dystrophy with progressive corneal thinning resulting in abnormal corneal shape and astigmatism. Corneal hydrops and rupture can occur and corneal transplant may become necessary. While keratoconus is rare in the general population occurring in about 1/2,000 individuals, it is more common in individuals with intellectual disability and syndromic conditions. Connective tissue abnormalities, most typically brittle cornea syndrome, have frequently been reported in association with keratoconus. Here, we report on bilateral keratoconus with acute hydrops in the left eye of a 24‐year‐old male with Costello syndrome. The patient was treated medically. After resolution of the hydrops, he had significant visual impairment from the resulting irregular astigmatism and scarring. This is the second report of keratoconus in Costello syndrome, suggesting an increased risk for this corneal dystrophy in individuals with Costello syndrome. Ongoing ophthalmological surveillance may be necessary for adult individuals with Costello syndrome, and apparent vision changes should be evaluated expediently. © 2013 Wiley Periodicals, Inc.

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PRDM5 promotes the proliferation and invasion of murine melanoma cells through up‐regulating JNK expression

et al. 2016

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PRDM (PRDI‐BF1 and RIZ domain‐containing) proteins constitute a family of zinc finger proteins and play important roles in multiple cellular processes by acting as epigenetic modifiers. PRDM5 is a recently identified member of the PRDM family and may function as a tumor suppressor in several types of cancer. However, the role of PRDM5 in murine melanoma remains largely unknown. In our study, effect of PRDM5 on murine melanoma cells was determined and results showed that PRDM5 overexpression significantly promoted proliferation, migration, and invasion of murine melanoma B16F10 cells. Consistently, silencing of PRDM5 expression significantly inhibited proliferation, invasion, and migration of B16F10 cells. In vivo study also showed that PRDM5 silencing significantly inhibited the growth and metastasis of melanoma in mice. PRDM5 was then found to increase the expression and activation of JNK in B16F10 cells. JNK silencing significantly reduced PRDM5‐mediated up‐regulation of JNK expression and blocked the PRDM5‐induced proliferation and invasion of B16F10 cells. To further verify the involvement of JNK signaling in PRDM5‐induced progression of B16F10 cells, a specific JNK inhibitor was employed to inhibit the JNK signaling pathway, and results showed that PRDM5‐induced proliferation and invasion of B16F10 cells were abolished. We conclude that PRDM5 promotes the proliferation and invasion of murine melanoma cells through up‐regulating JNK expression and strategies targeting PRDM5 may be promising for the therapy of melanoma.

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Mutations in PRDM5 in Brittle Cornea Syndrome Identify a Pathway Regulating Extracellular Matrix Development and Maintenance

Cited by 10 publications

References 0 publications

The Ehlers–Danlos syndromes, rare types

The Ehlers–Danlos syndromes, rare types

Keratoconus in Costello Syndrome

PRDM5 promotes the proliferation and invasion of murine melanoma cells through up‐regulating JNK expression

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