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PRPH2 mutation update: In silico assessment of 245 reported and 7 novel variants in patients with retinal disease
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  • Manon H.C.A Peeters,
  • Mubeen Khan,
  • Anoek A.M.B Rooijakkers,
  • Timo Mulders,
  • Lonneke Haer-Wigman,
  • Camiel Boon,
  • Caroline Klaver,
  • Ingeborgh van den Born,
  • Carel Hoyng,
  • Frans Cremers,
  • Anneke denHollander,
  • Claire-Marie Dhaenens,
  • Rob Collin
Manon H.C.A Peeters
Radboud university medical centre

Corresponding Author:[email protected]

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Mubeen Khan
Radboud Universiteit Donders Institute for Brain Cognition and Behaviour
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Anoek A.M.B Rooijakkers
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Timo Mulders
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Lonneke Haer-Wigman
Radboud university medical centre
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Camiel Boon
Leids Universitair Medisch Centrum
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Caroline Klaver
Erasmus MC
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Ingeborgh van den Born
The Rotterdam Eye Hospital
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Carel Hoyng
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Frans Cremers
Radboud University Nijmegen Medical Centre
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Anneke denHollander
Radboud University Medical Center
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Claire-Marie Dhaenens
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Rob Collin
Radboud university medical centre
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Mutations in PRPH2, encoding peripherin-2, are associated with the development of a wide variety of inherited retinal diseases (IRDs). To determine the causality of the many PRPH2 variants that have been discovered over the last decades, we surveyed all published PRPH2 variants up to July 2020, describing 720 index patients that in total carried 245 unique variants. In addition, we identified seven novel PRPH2 variants in eight additional index patients. The pathogenicity of all variants was determined using the ACMG guidelines. With this, 107 variants were classified as pathogenic, 92 as likely pathogenic, one as benign, and two as likely benign. The remaining 50 variants were classified as variants of uncertain significance. Interestingly, of the in total 252 PRPH2 variants, more than half (n=137) were missense variants. All variants were uploaded into the Leiden Open source Variation Database. Our study underscores the need of experimental assays for variants of unknown significance to improve pathogenicity classification, which is needed to better understand genotype-phenotype correlations, and in the long-term, hopefully also support the development of therapeutic strategies for patients with PRPH2-associated IRD.
26 Feb 2021Submitted to Human Mutation
04 Mar 2021Submission Checks Completed
04 Mar 2021Assigned to Editor
13 Mar 2021Reviewer(s) Assigned
16 May 2021Review(s) Completed, Editorial Evaluation Pending
18 May 2021Editorial Decision: Revise Minor
16 Jul 20211st Revision Received
22 Jul 2021Submission Checks Completed
22 Jul 2021Assigned to Editor
24 Jul 2021Reviewer(s) Assigned
13 Aug 2021Review(s) Completed, Editorial Evaluation Pending
17 Aug 2021Editorial Decision: Accept
Dec 2021Published in Human Mutation volume 42 issue 12 on pages 1521-1547. 10.1002/humu.24275