{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:28:00Z","timestamp":1790015280964,"version":"4.0.1"},"reference-count":97,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T00:00:00Z","timestamp":1726531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ryan Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Usher syndrome (USH) is an inherited disorder characterized by sensorineural hearing loss (SNHL), retinitis pigmentosa (RP)-related vision loss, and vestibular dysfunction. USH presents itself as three distinct clinical types, 1, 2, and 3, with no biomarker for early detection. This study aimed to explore whether microRNA (miRNA) expression in USH cell lines is dysregulated compared to the miRNA expression pattern in a cell line derived from a healthy human subject. Lymphocytes from USH patients and healthy individuals were isolated and transformed into stable cell lines using Epstein\u2013Barr virus (EBV). DNA from these cell lines was sequenced using a targeted panel to identify gene variants associated with USH types 1, 2, and 3. Microarray analysis was performed on RNA from both USH and control cell lines using NanoString miRNA microarray technology. Dysregulated miRNAs identified by the microarray were validated using droplet digital PCR technology. DNA sequencing revealed that two USH patients had USH type 1 with gene variants in USH1B (MYO7A) and USH1D (CDH23), while the other two patients were classified as USH type 2 (USH2A) and USH type 3 (CLRN-1), respectively. The NanoString miRNA microarray detected 92 differentially expressed miRNAs in USH cell lines compared to controls. Significantly altered miRNAs exhibited at least a twofold increase or decrease with a p value below 0.05. Among these miRNAs, 20 were specific to USH1, 14 to USH2, and 5 to USH3. Three miRNAs that are known as miRNA-183 family which are crucial for inner ear and retina development, have been significantly downregulated as compared to control cells. Subsequently, droplet digital PCR assays confirmed the dysregulation of the 12 most prominent miRNAs in USH cell lines. This study identifies several miRNA signatures in USH cell lines which may have potential utility in Usher syndrome identification.<\/jats:p>","DOI":"10.3390\/ijms25189993","type":"journal-article","created":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T01:52:31Z","timestamp":1726624351000},"page":"9993","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Genotype Characterization and MiRNA Expression Profiling in Usher Syndrome Cell Lines"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5951-5311","authenticated-orcid":false,"given":"Wesley A.","family":"Tom","sequence":"first","affiliation":[{"name":"Molecular Diagnostic Research Laboratory, Center for Sensory Neuroscience, Boys Town National Research Hospital, Omaha, NE 68010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0424-9423","authenticated-orcid":false,"given":"Dinesh S.","family":"Chandel","sequence":"additional","affiliation":[{"name":"Molecular Diagnostic Research Laboratory, Center for Sensory Neuroscience, Boys Town National Research Hospital, Omaha, NE 68010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Molecular Diagnostic Research Laboratory, Center for Sensory Neuroscience, Boys Town National Research Hospital, Omaha, NE 68010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Krzyzanowski","sequence":"additional","affiliation":[{"name":"Molecular Diagnostic Research Laboratory, Center for Sensory Neuroscience, Boys Town National Research Hospital, Omaha, NE 68010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nirmalee","family":"Fernando","sequence":"additional","affiliation":[{"name":"Molecular Diagnostic Research Laboratory, Center for Sensory Neuroscience, Boys Town National Research Hospital, Omaha, NE 68010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Appolinaire","family":"Olou","sequence":"additional","affiliation":[{"name":"Molecular Diagnostic Research Laboratory, Center for Sensory Neuroscience, Boys Town National Research Hospital, Omaha, NE 68010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Rohan","family":"Fernando","sequence":"additional","affiliation":[{"name":"Molecular Diagnostic Research Laboratory, Center for Sensory Neuroscience, Boys Town National Research Hospital, Omaha, NE 68010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Whatley, M., Francis, A., Ng, Z.Y., Khoh, X.E., Atlas, M.D., Dilley, R.J., and Wong, E.Y.M. (2020). Usher Syndrome: Genetics and Molecular Links of Hearing Loss and Directions for Therapy. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.565216"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1007\/s00439-022-02448-7","article-title":"The Genetic and Phenotypic Landscapes of Usher Syndrome: From Disease Mechanisms to a New Classification","volume":"141","author":"Delmaghani","year":"2022","journal-title":"Hum. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1097\/GIM.0b013e3181e5afb8","article-title":"Frequency of Usher Syndrome in Two Pediatric Populations: Implications for Genetic Screening of Deaf and Hard of Hearing Children","volume":"12","author":"Kimberling","year":"2010","journal-title":"Genet. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1093\/hmg\/ddi010","article-title":"Digenic Inheritance of Deafness Caused by Mutations in Genes Encoding Cadherin 23 and Protocadherin 15 in Mice and Humans","volume":"14","author":"Zheng","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2588","DOI":"10.1093\/hmg\/dds084","article-title":"Digenic Inheritance of Deafness Caused by 8J Allele of Myosin-VIIA and Mutations in Other Usher I Genes","volume":"21","author":"Zheng","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_6","unstructured":"Koenekoop, R.K., Arriaga, M.A., Trzupek, K.M., and Lentz, J.J. (2020). Usher Syndrome Type I. GeneReviews\u00ae, University of Washington."},{"key":"ref_7","unstructured":"(2024, September 09). MYO7A Myosin VIIA [Homo Sapiens (Human)]\u2014Gene\u2014NCBI, Available online: https:\/\/www.ncbi.nlm.nih.gov\/gene\/4647#gene-expression."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Miyoshi, T., Belyantseva, I.A., Sajeevadathan, M., and Friedman, T.B. (2024). Pathophysiology of Human Hearing Loss Associated with Variants in Myosins. Front. Physiol., 15.","DOI":"10.3389\/fphys.2024.1374901"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1042\/BST0391207","article-title":"The Many Different Cellular Functions of MYO7A in the Retina","volume":"39","author":"Williams","year":"2011","journal-title":"Biochem. Soc. Trans."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7924","DOI":"10.1167\/iovs.11-8313","article-title":"Retinal Disease Course in Usher Syndrome 1B due to MYO7A Mutations","volume":"52","author":"Jacobson","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.exer.2005.11.010","article-title":"Molecular Basis of Human Usher Syndrome: Deciphering the Meshes of the Usher Protein Network Provides Insights into the Pathomechanisms of the Usher Disease","volume":"83","author":"Reiners","year":"2006","journal-title":"Exp. Eye Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/83660","article-title":"Mutations in Cdh23, Encoding a New Type of Cadherin, Cause Stereocilia Disorganization in Waltzer, the Mouse Model for Usher Syndrome Type 1D","volume":"27","author":"Palma","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/S0955-0674(00)00137-X","article-title":"Cadherin-Mediated Adhesion at the Interneuronal Synapse","volume":"12","year":"2000","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5006","DOI":"10.1167\/iovs.03-0483","article-title":"Differential Distribution of Harmonin Isoforms and Their Possible Role in Usher-1 Protein Complexes in Mammalian Photoreceptor Cells","volume":"44","author":"Reiners","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_15","unstructured":"Adam, M.P., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., Bean, L.J., Gripp, K.W., and Amemiya, A. (1993). Usher Syndrome Type II. GeneReviews\u00ae, University of Washington."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"100229","DOI":"10.1016\/j.xhgg.2023.100229","article-title":"USH2A Variants Causing Retinitis Pigmentosa or Usher Syndrome Provoke Differential Retinal Phenotypes in Disease-Specific Organoids","volume":"4","author":"Erkilic","year":"2023","journal-title":"Hum. Genet. Genom. Adv."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4413","DOI":"10.1073\/pnas.0610950104","article-title":"Usherin Is Required for Maintenance of Retinal Photoreceptors and Normal Development of Cochlear Hair Cells","volume":"104","author":"Liu","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1038\/sj.ejhg.5200831","article-title":"USH3A Transcripts Encode Clarin-1, a Four-Transmembrane-Domain Protein with a Possible Role in Sensory Synapses","volume":"10","author":"Adato","year":"2002","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1167\/iovs.63.4.25","article-title":"Retinal Phenotype of Patients with CLRN1-Associated Usher 3A Syndrome in French Light4Deaf Cohort","volume":"63","author":"Smirnov","year":"2022","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"E1106","DOI":"10.1073\/pnas.1420955112","article-title":"Analysis of 13 Cell Types Reveals Evidence for the Expression of Numerous Novel Primate- and Tissue-Specific microRNAs","volume":"112","author":"Londin","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.brainres.2006.07.006","article-title":"MicroRNA Gene Expression in the Mouse Inner Ear","volume":"1111","author":"Weston","year":"2006","journal-title":"Brain Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1167\/iovs.06-0866","article-title":"Identification and Characterization of microRNAs Expressed in the Mouse Eye","volume":"48","author":"Karali","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1097\/MOO.0b013e32833e0601","article-title":"MicroRNAs in Hair Cell Development and Deafness","volume":"18","author":"Li","year":"2010","journal-title":"Curr. Opin. Otolaryngol. Head Neck Surg."},{"key":"ref_24","first-page":"165897","article-title":"MicroRNAs in the Neural Retina","volume":"2014","author":"Andreeva","year":"2014","journal-title":"Int. J. Genom."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ushakov, K., Rudnicki, A., and Avraham, K.B. (2013). MicroRNAs in Sensorineural Diseases of the Ear. Front. Mol. Neurosci., 6.","DOI":"10.3389\/fnmol.2013.00052"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7173","DOI":"10.1093\/nar\/gkv703","article-title":"The microRNA-183 Cluster: The Family That Plays Together Stays Together","volume":"43","author":"Dambal","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3254","DOI":"10.1523\/JNEUROSCI.4948-09.2010","article-title":"MicroRNA-183 Family Members Regulate Sensorineural Fates in the Inner Ear","volume":"30","author":"Li","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.gene.2018.10.075","article-title":"Role of microRNAs in Inner Ear Development and Hearing Loss","volume":"686","author":"Mittal","year":"2019","journal-title":"Gene"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6376","DOI":"10.1073\/pnas.1618757114","article-title":"miR-183\/96 Plays a Pivotal Regulatory Role in Mouse Photoreceptor Maturation and Maintenance","volume":"114","author":"Xiang","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1167\/iovs.61.3.12","article-title":"Ablation of Mature miR-183 Leads to Retinal Dysfunction in Mice","volume":"61","author":"Zhang","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"E507","DOI":"10.1073\/pnas.1212655110","article-title":"Inactivation of the microRNA-183\/96\/182 Cluster Results in Syndromic Retinal Degeneration","volume":"110","author":"Lumayag","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","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_33","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1136\/jmedgenet-2011-100262","article-title":"Allelic Hierarchy of CDH23 Mutations Causing Non-Syndromic Deafness DFNB12 or Usher Syndrome USH1D in Compound Heterozygotes","volume":"48","author":"Schultz","year":"2011","journal-title":"J. Med. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Al Dhahouri, N., Ali, A., Hertecant, J., and Al-Jasmi, F. (2021). Case Report: Reinterpretation and Reclassification of ARSB:P.Arg159Cys Variant Identified in an Emirati Patient with Hearing Loss Caused by a Pathogenic Variant in the CDH23 Gene. Front. Pediatr., 9.","DOI":"10.3389\/fped.2021.803732"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1086\/341558","article-title":"CDH23 Mutation and Phenotype Heterogeneity: A Profile of 107 Diverse Families with Usher Syndrome and Nonsyndromic Deafness","volume":"71","author":"Astuto","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/83667","article-title":"Mutation of CDH23, Encoding a New Member of the Cadherin Gene Family, Causes Usher Syndrome Type 1D","volume":"27","author":"Bolz","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s00439-014-1512-7","article-title":"Next-Generation Sequencing-Based Molecular Diagnosis of 82 Retinitis Pigmentosa Probands from Northern Ireland","volume":"134","author":"Zhao","year":"2015","journal-title":"Hum. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1089\/gtmb.2020.0153","article-title":"Screening Consanguineous Families for Hearing Loss Using the MiamiOtoGenes Panel","volume":"24","author":"Yan","year":"2020","journal-title":"Genet. Test. Mol. Biomark."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Svidnicki, M.C.C.M., Silva-Costa, S.M., Ramos, P.Z., dos Santos, N.Z.P., Martins, F.T.A., Castilho, A.M., and Sartorato, E.L. (2015). Screening of Genetic Alterations Related to Non-Syndromic Hearing Loss Using MassARRAY iPLEX\u00ae Technology. BMC Med. Genet., 16.","DOI":"10.1186\/s12881-015-0232-8"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"8488","DOI":"10.1167\/iovs.14-15169","article-title":"Targeted Exon Sequencing in Usher Syndrome Type I","volume":"55","author":"Bujakowska","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"E76","DOI":"10.1002\/humu.20780","article-title":"UMD-USHbases: A Comprehensive Set of Databases to Record and Analyse Pathogenic Mutations and Unclassified Variants in Seven Usher Syndrome Causing Genes","volume":"29","author":"Baux","year":"2008","journal-title":"Hum. Mutat."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1002\/humu.9526","article-title":"Usher Syndrome Type 1 due to Missense Mutations on Both CDH23 Alleles: Investigation of mRNA Splicing","volume":"29","author":"Becirovic","year":"2008","journal-title":"Hum. Mutat."},{"key":"ref_43","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_44","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s00439-016-1648-8","article-title":"Comprehensive Genetic Testing in the Clinical Evaluation of 1119 Patients with Hearing Loss","volume":"135","author":"Bierer","year":"2016","journal-title":"Hum. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.ophtha.2013.09.017","article-title":"Natural History and Retinal Structure in Patients with Usher Syndrome Type 1 Owing to MYO7A Mutation","volume":"121","author":"Lenassi","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1136\/jmedgenet-2011-100468","article-title":"Comprehensive Sequence Analysis of Nine Usher Syndrome Genes in the UK National Collaborative Usher Study","volume":"49","author":"Saihan","year":"2012","journal-title":"J. Med. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1167\/iovs.08-3122","article-title":"Disease Boundaries in the Retina of Patients with Usher Syndrome Caused by MYO7A Gene Mutations","volume":"50","author":"Jacobson","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4250","DOI":"10.1093\/nar\/gkm402","article-title":"Aberrant 5\u2032 Splice Sites in Human Disease Genes: Mutation Pattern, Nucleotide Structure and Comparison of Computational Tools That Predict Their Utilization","volume":"35","author":"Buratti","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1007\/s00439-004-1227-2","article-title":"Characterization of Usher Syndrome Type I Gene Mutations in an Usher Syndrome Patient Population","volume":"116","author":"Ouyang","year":"2005","journal-title":"Hum. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1006\/exer.2000.0863","article-title":"Evaluation of the Myosin VIIA Gene and Visual Function in Patients with Usher Syndrome Type I","volume":"71","author":"Bharadwaj","year":"2000","journal-title":"Exp. Eye Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1093\/hmg\/7.5.919","article-title":"Statistical Features of Human Exons and Their Flanking Regions","volume":"7","author":"Zhang","year":"1998","journal-title":"Hum. Mol. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1111\/j.1755-3768.2012.02397.x","article-title":"Extended Mutation Spectrum of Usher Syndrome in Finland","volume":"91","author":"Jalkanen","year":"2013","journal-title":"Acta Ophthalmol."},{"key":"ref_53","first-page":"1806","article-title":"Disease-Causing Mutations in the CLRN1 Gene Alter Normal CLRN1 Protein Trafficking to the Plasma Membrane","volume":"15","author":"Isosomppi","year":"2009","journal-title":"Mol. Vis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1086\/342098","article-title":"Usher Syndrome Type III: Revised Genomic Structure of the USH3 Gene and Identification of Novel Mutations","volume":"71","author":"Fields","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1086\/323610","article-title":"Mutations in a Novel Gene with Transmembrane Domains Underlie Usher Syndrome Type 3","volume":"69","author":"Joensuu","year":"2001","journal-title":"Am. J. Hum. Genet."},{"key":"ref_56","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_57","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1172\/JCI39715","article-title":"PDZD7 Is a Modifier of Retinal Disease and a Contributor to Digenic Usher Syndrome","volume":"120","author":"Ebermann","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/ejhg.2008.143","article-title":"An USH2A Founder Mutation Is the Major Cause of Usher Syndrome Type 2 in Canadians of French Origin and Confirms Common Roots of Quebecois and Acadians","volume":"17","author":"Ebermann","year":"2009","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5532","DOI":"10.1167\/iovs.08-2009","article-title":"Disease Course in Patients with Autosomal Recessive Retinitis Pigmentosa due to the USH2A Gene","volume":"49","author":"Sandberg","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.exer.2004.03.005","article-title":"Comprehensive Screening of the USH2A Gene in Usher Syndrome Type II and Non-Syndromic Recessive Retinitis Pigmentosa","volume":"79","author":"Seyedahmadi","year":"2004","journal-title":"Exp. Eye Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1086\/302855","article-title":"Genomic Structure and Identification of Novel Mutations in Usherin, the Gene Responsible for Usher Syndrome Type IIa","volume":"66","author":"Weston","year":"2000","journal-title":"Am. J. Hum. Genet."},{"key":"ref_62","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_63","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/sj.ejhg.5200491","article-title":"Identification of Novel USH2A Mutations: Implications for the Structure of USH2A Protein","volume":"8","author":"Dreyer","year":"2000","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.ijporl.2016.09.010","article-title":"Compound Heterozygous MYO7A Mutations Segregating Usher Syndrome Type 2 in a Han Family","volume":"90","author":"Zong","year":"2016","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Xing, D., Zhou, H., Yu, R., Wang, L., Hu, L., Li, Z., and Li, X. (2020). Targeted Exome Sequencing Identified a Novel USH2A Mutation in a Chinese Usher Syndrome Family: A Case Report. BMC Ophthalmol., 20.","DOI":"10.1186\/s12886-020-01711-7"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/ejhg.2010.140","article-title":"Alternative Splice Variants of the USH3A Gene Clarin 1 (CLRN1)","volume":"19","author":"Jalkanen","year":"2011","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1073\/pnas.1016646108","article-title":"miR-96 Regulates the Progression of Differentiation in Mammalian Cochlear Inner and Outer Hair Cells","volume":"108","author":"Kuhn","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1038\/ng.369","article-title":"An ENU-Induced Mutation of miR-96 Associated with Progressive Hearing Loss in Mice","volume":"41","author":"Lewis","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1093\/hmg\/ddr493","article-title":"A Novel Mutation within the MIR96 Gene Causes Non-Syndromic Inherited Hearing Loss in an Italian Family by Altering Pre-miRNA Processing","volume":"21","author":"Robusto","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/ng.355","article-title":"Mutations in the Seed Region of Human miR-96 Are Responsible for Nonsyndromic Progressive Hearing Loss","volume":"41","author":"Redshaw","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Xu, S., Coku, A., Muraleedharan, C.K., Harajli, A., Mishulin, E., Dahabra, C., Choi, J., Garcia, W.J., Webb, K., and Birch, D. (2020). Mutation Screening in the miR-183\/96\/182 Cluster in Patients with Inherited Retinal Dystrophy. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.619641"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Ji, H.-P., Xiong, Y., Song, W.-T., Zhang, E.-D., Gao, Z.-L., Yao, F., Su, T., Zhou, R.-R., and Xia, X.-B. (2017). MicroRNA-28 Potentially Regulates the Photoreceptor Lineage Commitment of M\u00fcller Glia-Derived Progenitors. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-11112-4"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1007\/s00405-017-4470-6","article-title":"MicroRNAs: Effective Elements in Ear-Related Diseases and Hearing Loss","volume":"274","author":"Ahmadinejad","year":"2017","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.heares.2015.08.003","article-title":"Analysis of Plasma microRNA Expression Profiles in Male Textile Workers with Noise-Induced Hearing Loss","volume":"333","author":"Ding","year":"2016","journal-title":"Hear. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1097\/WNR.0000000000001379","article-title":"miR-16-5p and miR-19b-3p Prevent Amyloid \u03b2-Induced Injury by Targeting BACE1 in SH-SY5Y Cells","volume":"31","author":"Zhang","year":"2020","journal-title":"Neuroreport"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Hong, E.H., Hwang, M., Yu, H., Park, H.-H., Cho, H., Koh, S.-H., and Shin, Y.U. (2022). Differential Expression of Aqueous Humor microRNAs in Central Retinal Vein Occlusion and Its Association with Matrix Metalloproteinases: A Pilot Study. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-20834-z"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Wang, D.-H., Gu, C., and Yuan, Y.-Z. (2022). Case Report: A Case of Cystoid Macular Edema in Retinitis Pigmentosa with Central Retinal Vein Occlusion. Front. Med., 9.","DOI":"10.3389\/fmed.2022.877429"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Almenar-P\u00e9rez, E., Sarr\u00eda, L., Nathanson, L., and Oltra, E. (2020). Assessing Diagnostic Value of microRNAs from Peripheral Blood Mononuclear Cells and Extracellular Vesicles in Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-58506-5"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"6889","DOI":"10.1128\/JVI.07056-11","article-title":"The Epstein-Barr Virus (EBV)-Induced Tumor Suppressor MicroRNA MiR-34a Is Growth Promoting in EBV-Infected B Cells","volume":"86","author":"Forte","year":"2012","journal-title":"J. Virol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Iizasa, H., Kim, H., Kartika, A.V., Kanehiro, Y., and Yoshiyama, H. (2020). Role of Viral and Host microRNAs in Immune Regulation of Epstein-Barr Virus-Associated Diseases. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00367"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"10436","DOI":"10.1128\/JVI.00752-08","article-title":"Epstein-Barr Virus-Induced miR-155 Attenuates NF-kappaB Signaling and Stabilizes Latent Virus Persistence","volume":"82","author":"Lu","year":"2008","journal-title":"J. Virol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.gene.2012.12.009","article-title":"Regulation of the MIR155 Host Gene in Physiological and Pathological Processes","volume":"532","author":"Elton","year":"2013","journal-title":"Gene"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Souza, O.F., and Popi, A.F. (2022). Role of microRNAs in B-Cell Compartment: Development, Proliferation and Hematological Diseases. Biomedicines, 10.","DOI":"10.3390\/biomedicines10082004"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Nail, H.M., Chiu, C.-C., Leung, C.-H., Ahmed, M.M.M., and Wang, H.-M.D. (2023). Exosomal miRNA-Mediated Intercellular Communications and Immunomodulatory Effects in Tumor Microenvironments. J. Biomed. Sci., 30.","DOI":"10.1186\/s12929-023-00964-w"},{"key":"ref_85","unstructured":"(2023, July 11). Human Genome Overview\u2014Genome Reference Consortium, Available online: https:\/\/www.ncbi.nlm.nih.gov\/grc\/human."},{"key":"ref_86","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_87","doi-asserted-by":"crossref","first-page":"giab008","DOI":"10.1093\/gigascience\/giab008","article-title":"Twelve Years of SAMtools and BCFtools","volume":"10","author":"Danecek","year":"2021","journal-title":"GigaScience"},{"key":"ref_88","first-page":"e1672v2","article-title":"Sentieon DNA Pipeline for Variant Detection\u2014Software-Only Solution, over 20\u00d7 Faster than GATK 3.3 with Identical Results","volume":"4","author":"Weber","year":"2016","journal-title":"PeerJ PrePrints"},{"key":"ref_89","unstructured":"(2017). Standard No. VarSeqTM [Software]. Available online: https:\/\/www.Goldenhelix.com."},{"key":"ref_90","unstructured":"R Core Team (2017). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1093\/bioinformatics\/btz647","article-title":"NACHO: An R Package for Quality Control of NanoString nCounter Data","volume":"36","author":"Canouil","year":"2020","journal-title":"Bioinformatics"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Campomenosi, P., Gini, E., Noonan, D.M., Poli, A., D\u2019Antona, P., Rotolo, N., Dominioni, L., and Imperatori, A. (2016). A Comparison between Quantitative PCR and Droplet Digital PCR Technologies for Circulating microRNA Quantification in Human Lung Cancer. BMC Biotechnol., 16.","DOI":"10.1186\/s12896-016-0292-7"},{"key":"ref_93","unstructured":"Yan, L. (2023, December 23). Ggvenn: Draw Venn Diagram by \u201cGgplot2\u201d. R Package Version 0.1.9. CRAN, Available online: https:\/\/cran.r-project.org\/web\/packages\/ggvenn\/index.html."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e43","DOI":"10.1002\/imt2.43","article-title":"Complex Heatmap Visualization","volume":"1","author":"Gu","year":"2022","journal-title":"iMeta"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3201","DOI":"10.21105\/joss.03201","article-title":"microViz: An R Package for Microbiome Data Visualization and Statistics","volume":"6","author":"Barnett","year":"2021","journal-title":"J. Open Source Softw."},{"key":"ref_96","unstructured":"Anderson, M.J. (2017). Permutational Multivariate Analysis of Variance (PERMANOVA). Wiley StatsRef: Statistics Reference Online, John Wiley & Sons, Ltd."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1111\/j.1654-1103.2003.tb02228.x","article-title":"VEGAN, a Package of R Functions for Community Ecology","volume":"14","author":"Dixon","year":"2003","journal-title":"J. Veg. Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/18\/9993\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:57:42Z","timestamp":1760111862000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/18\/9993"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,17]]},"references-count":97,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["ijms25189993"],"URL":"https:\/\/doi.org\/10.3390\/ijms25189993","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,17]]}}}