High prevalence of mutations affecting the splicing process in a Spanish cohort with autosomal dominant retinitis pigmentosa

Scientific Reports
Maitane Ezquerra-InchaustiJavier Ruiz-Ederra

Abstract

Retinitis pigmentosa is the most frequent group of inherited retinal dystrophies. It is highly heterogeneous, with more than 80 disease-causing genes 27 of which are known to cause autosomal dominant RP (adRP), having been identified. In this study a total of 29 index cases were ascertained based on a family tree compatible with adRP. A custom panel of 31 adRP genes was analysed by targeted next-generation sequencing using the Ion PGM platform in combination with Sanger sequencing. This allowed us to detect putative disease-causing mutations in 14 out of the 29 (48.28%) families analysed. Remarkably, around 38% of all adRP cases analysed showed mutations affecting the splicing process, mainly due to mutations in genes coding for spliceosome factors (SNRNP200 and PRPF8) but also due to splice-site mutations in RHO. Twelve of the 14 mutations found had been reported previously and two were novel mutations found in PRPF8 in two unrelated patients. In conclusion, our results will lead to more accurate genetic counselling and will contribute to a better characterisation of the disease. In addition, they may have a therapeutic impact in the future given the large number of studies currently underway based on targeted RNA splicing for...Continue Reading

References

May 1, 1987·Journal of General Microbiology·S P ChampeA Chang
Aug 26, 1998·Current Biology : CB·P L Raghunathan, C Guthrie
Oct 13, 2006·Orphanet Journal of Rare Diseases·Christian Hamel
Nov 23, 2006·Lancet·Dyonne T HartongThaddeus P Dryja
Feb 26, 2009·Cell·Markus C WahlReinhard Lührmann
Jun 16, 2009·Nature Structural & Molecular Biology·Lingdi ZhangRui Zhao
Aug 3, 2010·Nature Methods·Jana Marie SchwarzDominik Seelow
Sep 24, 2010·Investigative Ophthalmology & Visual Science·Sara J BowneStephen P Daiger
Feb 18, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Esther GlausJohn Neidhardt
Jul 24, 2012·Trends in Molecular Medicine·Ravi K Singh, Thomas A Cooper
Oct 2, 2012·Vision Research·Ander AnasagastiJavier Ruiz-Ederra
Oct 12, 2012·PloS One·Yongwook ChoiAgnes P Chan
Mar 21, 2013·Wiley Interdisciplinary Reviews. RNA·Mallory A HavensMichelle L Hastings
May 8, 2013·Clinical Genetics·M M Liu, D J Zack
Aug 14, 2013·The Journal of Biological Chemistry·T J Hollingsworth, Alecia K Gross
Dec 5, 2013·Human Mutation·Zuzana CvačkováDavid Staněk
Jan 15, 2014·Experimental Eye Research·Ander AnasagastiJavier Ruiz-Ederra
Jan 15, 2014·Human Molecular Genetics·Xue ChenChen Zhao
Mar 13, 2014·JAMA : the Journal of the American Medical Association·Frederick E DeweyThomas Quertermous
Sep 6, 2014·Investigative Ophthalmology & Visual Science·Lori S SullivanStephen P Daiger
Oct 12, 2014·Cold Spring Harbor Perspectives in Medicine·Stephen P DaigerLori S Sullivan
Oct 16, 2014·Investigative Ophthalmology & Visual Science·Feng WangRui Chen
Jan 27, 2015·Molecular Therapy : the Journal of the American Society of Gene Therapy·Adeline BergerAlexis-Pierre Bemelmans
Feb 24, 2015·Investigative Ophthalmology & Visual Science·Patricia Fernandez-San JoseCarmen Ayuso
Apr 22, 2015·Nucleic Acids Research·Roberto AlonsoJoaquin Dopazo
Oct 16, 2015·Scientific Reports·Yuan LiuChen Zhao
Nov 26, 2015·Nature Reviews. Genetics·Marina M Scotti, Maurice S Swanson
Jan 1, 2016·Investigative Ophthalmology & Visual Science·Razek Georges CoussaRobert K Koenekoop
May 11, 2016·Ophthalmic Research·Olatz BarandikaJavier Ruiz-Ederra
Jun 16, 2016·RNA Biology·Šárka Růžičková, David Staněk

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Citations

Apr 13, 2019·Clinical & Experimental Ophthalmology·Johannes BirtelPeter Charbel Issa
May 28, 2019·International Journal of Molecular Sciences·Michalitsa DiakatouVasiliki Kalatzis
Jul 2, 2019·Investigative Ophthalmology & Visual Science·Christina Gerth-KahlertWolfgang Berger
Aug 25, 2020·Translational Vision Science & Technology·Debra A ThompsonUNKNOWN Monaciano Consortium
Jun 2, 2021·Biochemical Society Transactions·Dale W MaxwellKathryn E Hentges

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Methods Mentioned

BETA
antisense oligonucleotides
PCR
chips

Software Mentioned

Ion PGM System
MutationTaster
Torrent Suite
BioEdit Sequence Alignment Editor
SIFT
Polyphen2
Ion Torrent
PROVEAN
GVGD
Ion AmpliSeq Primer Pools

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