{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T03:22:22Z","timestamp":1783567342769,"version":"3.55.0"},"reference-count":52,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T00:00:00Z","timestamp":1623715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007214","name":"Velux Stiftung","doi-asserted-by":"publisher","award":["1129"],"award-info":[{"award-number":["1129"]}],"id":[{"id":"10.13039\/100007214","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fighting Blindness Ireland","award":["FB18CRE"],"award-info":[{"award-number":["FB18CRE"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A substantial proportion of subjects with autosomal recessive retinitis pigmentosa (arRP) or Usher syndrome type II (USH2) lacks a genetic diagnosis due to incomplete USH2A screening in the early days of genetic testing. These cases lack eligibility for optimal genetic counseling and future therapy. USH2A defects are the most frequent cause of USH2 and are also causative in individuals with arRP. Therefore, USH2A is an important target for genetic screening. The aim of this study was to assess unscreened or incompletely screened and unexplained USH2 and arRP cases for (likely) pathogenic USH2A variants. Molecular inversion probe (MIP)-based sequencing was performed for the USH2A exons and their flanking regions, as well as published deep-intronic variants. This was done to identify single nucleotide variants (SNVs) and copy number variants (CNVs) in 29 unscreened or partially pre-screened USH2 and 11 partially pre-screened arRP subjects. In 29 out of these 40 cases, two (likely) pathogenic variants were successfully identified. Four of the identified SNVs and one CNV were novel. One previously identified synonymous variant was demonstrated to affect pre-mRNA splicing. In conclusion, genetic diagnoses were obtained for a majority of cases, which confirms that MIP-based sequencing is an effective screening tool for USH2A. Seven unexplained cases were selected for future analysis with whole genome sequencing.<\/jats:p>","DOI":"10.3390\/ijms22126419","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T21:24:29Z","timestamp":1623792269000},"page":"6419","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Molecular Inversion Probe-Based Sequencing of USH2A Exons and Splice Sites as a Cost-Effective Screening Tool in USH2 and arRP Cases"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5677-9258","authenticated-orcid":false,"given":"Janine","family":"Reurink","sequence":"first","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 Nijmegen, The Netherlands"},{"name":"Donders Institute for Brain Cognition and Behaviour, Radboud University Medical Center, 6500 Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3423-2542","authenticated-orcid":false,"given":"Adrian","family":"Dockery","sequence":"additional","affiliation":[{"name":"The School of Genetics & Microbiology, Trinity College Dublin, D02 VF25 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3454-8002","authenticated-orcid":false,"given":"Dominika","family":"Ozi\u0119b\u0142o","sequence":"additional","affiliation":[{"name":"Department of Genetics, Institute of Physiology and Pathology of Hearing, 02-042 Warsaw\/Kajetany, Poland"},{"name":"Postgraduate School of Molecular Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9959-1992","authenticated-orcid":false,"given":"G. Jane","family":"Farrar","sequence":"additional","affiliation":[{"name":"The School of Genetics & Microbiology, Trinity College Dublin, D02 VF25 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4216-9141","authenticated-orcid":false,"given":"Monika","family":"O\u0142dak","sequence":"additional","affiliation":[{"name":"Department of Genetics, Institute of Physiology and Pathology of Hearing, 02-042 Warsaw\/Kajetany, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7884-0067","authenticated-orcid":false,"given":"Jacoline B.","family":"ten Brink","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam, 1105 Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6333-9576","authenticated-orcid":false,"given":"Arthur A.","family":"Bergen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam, 1105 Amsterdam, The Netherlands"},{"name":"Department of Ophthalmology, Amsterdam UMC, University of Amsterdam, 1105 Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4350-8106","authenticated-orcid":false,"given":"Tuula","family":"Rinne","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3877-6328","authenticated-orcid":false,"given":"Helger G.","family":"Yntema","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 Nijmegen, The Netherlands"},{"name":"Donders Institute for Brain Cognition and Behaviour, Radboud University Medical Center, 6500 Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5517-9683","authenticated-orcid":false,"given":"Ronald J. E.","family":"Pennings","sequence":"additional","affiliation":[{"name":"Donders Institute for Brain Cognition and Behaviour, Radboud University Medical Center, 6500 Nijmegen, The Netherlands"},{"name":"Department of Otorhinolaryngology, Radboud University Medical Center, 6500 Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6375-3339","authenticated-orcid":false,"given":"L. Ingeborgh","family":"van den Born","sequence":"additional","affiliation":[{"name":"The Rotterdam Eye Hospital, 3000 Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6069-3847","authenticated-orcid":false,"given":"Marco","family":"Aben","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3980-4220","authenticated-orcid":false,"given":"Jaap","family":"Oostrik","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Radboud University Medical Center, 6500 Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9824-6559","authenticated-orcid":false,"given":"Hanka","family":"Venselaar","sequence":"additional","affiliation":[{"name":"Centre for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6500 Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4903-8232","authenticated-orcid":false,"given":"Astrid S.","family":"Plomp","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam, 1105 Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0276-5480","authenticated-orcid":false,"given":"M. Imran","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5702-3460","authenticated-orcid":false,"given":"Erwin","family":"van Wijk","sequence":"additional","affiliation":[{"name":"Donders Institute for Brain Cognition and Behaviour, Radboud University Medical Center, 6500 Nijmegen, The Netherlands"},{"name":"Department of Otorhinolaryngology, Radboud University Medical Center, 6500 Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4954-5592","authenticated-orcid":false,"given":"Frans P. M.","family":"Cremers","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 Nijmegen, The Netherlands"},{"name":"Donders Institute for Brain Cognition and Behaviour, Radboud University Medical Center, 6500 Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9038-0067","authenticated-orcid":false,"given":"Susanne","family":"Roosing","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 Nijmegen, The Netherlands"},{"name":"Donders Institute for Brain Cognition and Behaviour, Radboud University Medical Center, 6500 Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0841-8693","authenticated-orcid":false,"given":"Hannie","family":"Kremer","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 Nijmegen, The Netherlands"},{"name":"Donders Institute for Brain Cognition and Behaviour, Radboud University Medical Center, 6500 Nijmegen, The Netherlands"},{"name":"Department of Otorhinolaryngology, Radboud University Medical Center, 6500 Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,15]]},"reference":[{"key":"ref_1","unstructured":"Daiger, S.R., Greenberg, J., Christoffels, A., and Hide, W. (2021, March 09). RetNet, the Retinal Information Network. Available online: https:\/\/sph.uth.edu\/RetNet\/."},{"key":"ref_2","first-page":"1","article-title":"Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications","volume":"11","author":"Gordo","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1016\/j.ophtha.2017.04.008","article-title":"Clinically Focused Molecular Investigation of 1000 Consecutive Families with Inherited Retinal Disease","volume":"124","author":"Stone","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1097\/MAO.0000000000002054","article-title":"Genetics of Usher Syndrome: New Insights from a Meta-analysis","volume":"40","author":"Jouret","year":"2019","journal-title":"Otol. Neurotol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1136\/jmg.2009.075143","article-title":"Novel mutations in the long isoform of the USH2A gene in patients with Usher syndrome type II or non-syndromic retinitis pigmentosa","volume":"47","author":"McGee","year":"2010","journal-title":"J. Med. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"108330","DOI":"10.1016\/j.exer.2020.108330","article-title":"USH2A-retinopathy: From genetics to therapeutics","volume":"201","author":"Toualbi","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_7","first-page":"223","article-title":"Population genetic studies of retinitis pigmentosa","volume":"32","author":"Boughman","year":"1980","journal-title":"Am. J. Hum. Genet."},{"key":"ref_8","first-page":"153","article-title":"Epidemiology and prevalence of hereditary retinal dystrophies in the Northern France","volume":"14","author":"Puech","year":"1991","journal-title":"J. Fr. Ophtalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1111\/j.1399-0004.1997.tb02480.x","article-title":"The prevalence of Usher syndrome and other retinal dystrophy-hearing impairment associations","volume":"51","author":"Rosenberg","year":"2008","journal-title":"Clin. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1007\/s00417-002-0485-8","article-title":"Prevalence and geographical distribution of Usher syndrome in Germany","volume":"240","author":"Spandau","year":"2002","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1086\/383096","article-title":"Identification of 51 Novel Exons of the Usher Syndrome Type 2A (USH2A) Gene That Encode Multiple Conserved Functional Domains and That Are Mutated in Patients with Usher Syndrome Type II","volume":"74","author":"Pennings","year":"2004","journal-title":"Am. J. Hum. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3921","DOI":"10.1093\/hmg\/ddi416","article-title":"Usherin, the defective protein in Usher syndrome type IIA, is likely to be a component of interstereocilia ankle links in the inner ear sensory cells","volume":"14","author":"Adato","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1126\/science.280.5370.1753","article-title":"Mutation of a Gene Encoding a Protein with Extracellular Matrix Motifs in Usher Syndrome Type IIa","volume":"280","author":"Eudy","year":"1998","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1136\/jmg.2006.044784","article-title":"Development of a genotyping microarray for Usher syndrome","volume":"44","author":"Cremers","year":"2006","journal-title":"J. Med. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Dulla, K., Slijkerman, R., van Diepen, H.C., Albert, S., Dona, M., Beumer, W., Turunen, J.J., Chan, H.L., Schulkens, I.A., and Vorthoren, L. (2021). Antisense oligonucleotide-based treatment of retinitis pigmentosa caused by USH2A exon 13 mutations. Mol. Ther.","DOI":"10.1101\/2020.10.06.320499"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1002\/humu.21634","article-title":"Usher syndrome type 2 caused by activation of an USH2A pseudoexon: Implications for diagnosis and therapy","volume":"33","author":"Besnard","year":"2012","journal-title":"Hum. Mutat."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e381","DOI":"10.1038\/mtna.2016.89","article-title":"Antisense Oligonucleotide-based Splice Correction for USH2A-associated Retinal Degeneration Caused by a Frequent Deep-intronic Mutation","volume":"5","author":"Slijkerman","year":"2016","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1002\/humu.22926","article-title":"Whole USH2A Gene Sequencing Identifies Several New Deep Intronic Mutations","volume":"37","author":"Liquori","year":"2016","journal-title":"Hum. Mutat."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"16783","DOI":"10.1038\/s41598-017-16846-9","article-title":"Combined genetic approaches yield a 48% diagnostic rate in a large cohort of French hearing-impaired patients","volume":"7","author":"Baux","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/nbt821","article-title":"Multiplexed genotyping with sequence-tagged molecular inversion probes","volume":"21","author":"Hardenbol","year":"2003","journal-title":"Nat. Biotechnol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1126\/science.1227764","article-title":"Multiplex Targeted Sequencing Identifies Recurrently Mutated Genes in Autism Spectrum Disorders","volume":"338","author":"Vives","year":"2012","journal-title":"Science"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1002\/humu.21193","article-title":"Ex vivo splicing assays of mutations at noncanonical positions of splice sites in USHER genes","volume":"31","author":"Baux","year":"2010","journal-title":"Hum. Mutat."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1002\/humu.21255","article-title":"Nasal epithelial cells are a reliable source to study splicing variants in Usher syndrome","volume":"31","author":"Besnard","year":"2010","journal-title":"Hum. Mutat."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1002\/humu.22608","article-title":"Enrichment of LOVD-USHbases with 152 USH2A Genotypes Defines an Extensive Mutational Spectrum and Highlights Missense Hotspots","volume":"35","author":"Baux","year":"2014","journal-title":"Hum. Mutat."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1002\/humu.20513","article-title":"Molecular and in silico analyses of the full-length isoform of usherin identify new pathogenic alleles in Usher type II patients","volume":"28","author":"Baux","year":"2007","journal-title":"Hum. Mutat."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1038\/ejhg.2015.54","article-title":"Partial USH2A deletions contribute to Usher syndrome in Denmark","volume":"23","author":"Dad","year":"2015","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1038\/s41436-020-0759-8","article-title":"Copy-number variation contributes 9% of pathogenicity in the inherited retinal degenerations","volume":"22","author":"Zampaglione","year":"2020","journal-title":"Genet. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5857","DOI":"10.1073\/pnas.95.11.5857","article-title":"SMART, a simple modular architecture research tool: Identification of signaling domains","volume":"95","author":"Schultz","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.ajhg.2018.02.008","article-title":"Identification and Rescue of Splice Defects Caused by Two Neighboring Deep-Intronic ABCA4 Mutations Underlying Stargardt Disease","volume":"102","author":"Albert","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1038\/ejhg.2016.99","article-title":"An innovative strategy for the molecular diagnosis of Usher syndrome identifies causal biallelic mutations in 93% of European patients","volume":"24","author":"Bonnet","year":"2016","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_31","first-page":"444","article-title":"A structural variation reference for medical and population genetics","volume":"581","author":"Collins","year":"2020","journal-title":"Nat. Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"D941","DOI":"10.1093\/nar\/gkz836","article-title":"The International Genome Sample Resource (IGSR) collection of open human genomic variation resources","volume":"48","author":"Fairley","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"107769","DOI":"10.1016\/j.heares.2019.07.006","article-title":"Next generation sequencing study in a cohort of Italian patients with syndromic hearing loss","volume":"381","author":"Lenarduzzi","year":"2019","journal-title":"Hear. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1002\/humu.9524","article-title":"Spectrum of USH2A mutations in Scandinavian patients with Usher syndrome type II","volume":"29","author":"Dreyer","year":"2008","journal-title":"Hum. Mutat."},{"key":"ref_35","unstructured":"Karczewski, K.J., Francioli, L.C., Tiao, G., Cummings, B.B., Alf\u00f6ldi, J., Wang, Q., Collins, R.L., Laricchia, K.M., Ganna, A., and Birnbaum, D.P. (2019). Variation across 141,456 human exomes and genomes reveals the spectrum of loss-of-function intolerance across human protein-coding genes. bioRxiv, 531210."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1126\/science.185.4154.862","article-title":"Amino Acid Difference Formula to Help Explain Protein Evolution","volume":"185","author":"Grantham","year":"1974","journal-title":"Science"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/ng.2892","article-title":"A general framework for estimating the relative pathogenicity of human genetic variants","volume":"46","author":"Kircher","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1101\/gr.097857.109","article-title":"Detection of nonneutral substitution rates on mammalian phylogenies","volume":"20","author":"Pollard","year":"2009","journal-title":"Genome Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1101\/gr.176601","article-title":"Predicting Deleterious Amino Acid Substitutions","volume":"11","author":"Ng","year":"2001","journal-title":"Genome Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nmeth.2890","article-title":"MutationTaster2: Mutation prediction for the deep-sequencing age","volume":"11","author":"Schwarz","year":"2014","journal-title":"Nat. Methods"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-Wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.cell.2018.12.015","article-title":"Predicting Splicing from Primary Sequence with Deep Learning","volume":"176","author":"Jaganathan","year":"2019","journal-title":"Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1038\/s41436-020-0787-4","article-title":"Resolving the dark matter of ABCA4 for 1054 Stargardt disease probands through integrated genomics and transcriptomics","volume":"22","author":"Khan","year":"2020","journal-title":"Genet. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1016\/j.ophtha.2016.01.053","article-title":"Photoreceptor Progenitor mRNA Analysis Reveals Exon Skipping Resulting from the ABCA4 c5461-10T\u2192C Mutation in Stargardt Disease","volume":"123","author":"Sangermano","year":"2016","journal-title":"Ophthalmology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1002\/prot.10104","article-title":"Increasing the precision of comparative models with YASARA NOVA\u2014A self-parameterizing force field","volume":"47","author":"Krieger","year":"2002","journal-title":"Proteins Struct. Funct. Bioinform."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/0263-7855(90)80070-V","article-title":"WHAT IF: A molecular modeling and drug design program","volume":"8","author":"Vriend","year":"1990","journal-title":"J. Mol. Graph."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1093\/protein\/gzv002","article-title":"Structural and dynamic properties that govern the stability of an engineered fibronectin type III domain","volume":"28","author":"Porebski","year":"2015","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"14634","DOI":"10.1073\/pnas.1311000110","article-title":"Insights into Eph receptor tyrosine kinase activation from crystal structures of the EphA4 ectodomain and its complex with ephrin-A5","volume":"110","author":"Xu","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6926","DOI":"10.1038\/ncomms7926","article-title":"Mechanisms of splicing-dependent trans-synaptic adhesion by PTP\u03b4\u2013IL1RAPL1\/IL-1RAcP for synaptic differentiation","volume":"6","author":"Yamagata","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1107\/S2059798320003885","article-title":"Crystal and solution structures of fragments of the human leucocyte common antigen-related protein","volume":"76","author":"Vilstrup","year":"2020","journal-title":"Acta Crystallogr. Sect. D Struct. Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/12\/6419\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:16:33Z","timestamp":1760163393000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/12\/6419"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,15]]},"references-count":52,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["ijms22126419"],"URL":"https:\/\/doi.org\/10.3390\/ijms22126419","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,15]]}}}