Expression ofPRPF31mRNA in Patients with Autosomal Dominant Retinitis Pigmentosa: A Molecular Clue for Incomplete Penetrance?

2003 ◽  
Vol 44 (10) ◽  
pp. 4204 ◽  
Author(s):  
Eranga N. Vithana ◽  
Leen Abu-Safieh ◽  
Lucia Pelosini ◽  
Elizabeth Winchester ◽  
Dan Hornan ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Autosomal Dominant ◽  
Incomplete Penetrance ◽  
Autosomal Dominant Retinitis Pigmentosa

scholarly journals A combined in silico, in vitro and clinical approach to characterise novel pathogenic missense variants in PRPF31 in retinitis pigmentosa

2018 ◽  
Author(s):  
Gabrielle Wheway ◽  
Liliya Nazlamova ◽  
Nervine Meshad ◽  
Samantha Hunt ◽  
Nicola Jackson ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
In Silico ◽  
Autosomal Dominant ◽  
Missense Variant ◽  
Incomplete Penetrance ◽  
Clinical Approach ◽  
Loss Of Function ◽  
Autosomal Dominant Retinitis Pigmentosa ◽  
Missense Variants

AbstractAt least six different proteins of the spliceosome, including PRPF3, PRPF4, PRPF6, PRPF8, PRPF31 and SNRNP200, are mutated in autosomal dominant retinitis pigmentosa (adRP). These proteins have recently been shown to localise to the base of the connecting cilium of the retinal photoreceptor cells, elucidating this form of RP as a retinal ciliopathy. In the case of loss-of-function variants in these genes, pathogenicity can easily be ascribed. In the case of missense variants, this is more challenging. Furthermore, the exact molecular mechanism of disease in this form of RP remains poorly understood.In this paper we take advantage of the recently published cryo EM-resolved structure of the entire human spliceosome, to predict the effect of a novel missense variant in one component of the spliceosome; PRPF31, found in a patient attending the genetics eye clinic at Bristol Eye Hospital. Monoallelic variants in PRPF31 are a common cause of autosomal dominant retinitis pigmentosa (adRP) with incomplete penetrance. We use in vitro studies to confirm pathogenicity of this novel variant PRPF31 c.341T>A, p.Ile114Asn.This work demonstrates how in silico modelling of structural effects of missense variants on cryo-EM resolved protein complexes can contribute to predicting pathogenicity of novel variants, in combination with in vitro and clinical studies. It is currently a considerable challenge to assign pathogenic status to missense variants in these proteins.

Nonallelic Heterogeneity in Autosomal Dominant Retinitis Pigmentosa with Incomplete Penetrance

Genomics ◽  
1994 ◽  
Vol 22 (3) ◽  
pp. 659-660 ◽  
Author(s):  
Stella K. Kim ◽  
Jonathan L. Haines ◽  
Eliot L. Betson ◽  
Thaddeus P. Dryja
Keyword(s):  
Retinitis Pigmentosa ◽  
Autosomal Dominant ◽  
Incomplete Penetrance ◽  
Autosomal Dominant Retinitis Pigmentosa

Autosomal Dominant Retinitis Pigmentosa with Intrafamilial Variability and Incomplete Penetrance in Two Families Carrying Mutations inPRPF8

2011 ◽  
Vol 52 (13) ◽  
pp. 9304 ◽  
Author(s):  
Cécilia G. Maubaret ◽  
Veronika Vaclavik ◽  
Rajarshi Mukhopadhyay ◽  
Naushin H. Waseem ◽  
Amanda Churchill ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Autosomal Dominant ◽  
Incomplete Penetrance ◽  
Autosomal Dominant Retinitis Pigmentosa ◽  
Intrafamilial Variability
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