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The duplication includes two entire genes, PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), in addition to four uncharacterized long non-coding (lnc) RNA genes and part of a novel protein-coding gene. Quantitative analysis of mRNA expression in blood samples revealed selective overexpression of CNRIP1 and of two lncRNA genes (LOC107985892 and LOC102724389) in all affected members tested, but not in unaffected ones. Qualitative analysis of mRNA expression identified also fusion transcripts involving parts of PPP3R1, CNRIP1 and an intergenic region between PLEK and CNRIP1, in the blood of all carriers of the duplication, but were heterogeneous in nature. By in situ hybridization and immunofluorescence, we showed that Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea including the spiral ganglion neurons, suggesting changes in expression levels of these genes in the hearing organ could underlie the DFNA58 form of deafness. Our study highlights the value of studying rare genomic events leading to HL, such as copy number variations. Further studies will be required to determine which of these genes, either coding proteins or non-coding RNAs, is or are responsible for DFNA58 HL.<\/jats:p>","DOI":"10.1093\/hmg\/ddaa075","type":"journal-article","created":{"date-parts":[[2020,4,22]],"date-time":"2020-04-22T03:20:32Z","timestamp":1587525632000},"page":"1520-1536","source":"Crossref","is-referenced-by-count":16,"title":["A rare genomic duplication in 2p14 underlies autosomal dominant hearing loss DFNA58"],"prefix":"10.1093","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7495-9789","authenticated-orcid":false,"given":"Karina","family":"Lezirovitz","sequence":"first","affiliation":[{"name":"Otorhinolaryngology\/LIM32, Hospital das Cl\u00ednicas HCFMUSP, Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-000, Brazil"},{"name":"Departamento de Otorrinolaringologia, Faculdade de Medicina FMUSP, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05403-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gleiciele A","family":"Vieira-Silva","sequence":"first","affiliation":[{"name":"Otorhinolaryngology\/LIM32, Hospital das Cl\u00ednicas HCFMUSP, Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-000, Brazil"},{"name":"Departamento de Otorrinolaringologia, Faculdade de Medicina FMUSP, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05403-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana C","family":"Batissoco","sequence":"first","affiliation":[{"name":"Otorhinolaryngology\/LIM32, Hospital das Cl\u00ednicas HCFMUSP, Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-000, Brazil"},{"name":"Departamento de Otorrinolaringologia, Faculdade de Medicina FMUSP, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05403-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D\u00e9bora","family":"Levy","sequence":"first","affiliation":[{"name":"Lipids, Oxidation, and Cell Biology Group, Head, Laboratory of Immunology (LIM19), Heart Institute (InCor), Hospital das Cl\u00ednicas HCFMUSP, Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05403-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joao P","family":"Kitajima","sequence":"first","affiliation":[{"name":"Mendelics Genomic Analysis, S\u00e3o Paulo 04013-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alix","family":"Trouillet","sequence":"first","affiliation":[{"name":"Department of Otolaryngology - 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Bull."},{"key":"2020060308400264000_ref10","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.neuron.2010.10.011","article-title":"Hearing impairment: a panoply of genes and functions","volume":"68","author":"Dror","year":"2010","journal-title":"Neuron"},{"key":"2020060308400264000_ref11","article-title":"(1\/2020) hereditary hearing loss homepage","author":"Van Camp"},{"key":"2020060308400264000_ref12","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1146\/annurev-genet-102108-134135","article-title":"Hearing loss: mechanisms revealed by genetics and cell biology","volume":"43","author":"Dror","year":"2009","journal-title":"Annu. Rev. Genet."},{"key":"2020060308400264000_ref13","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1146\/annurev-physiol-012110-142228","article-title":"How the genetics of deafness illuminates auditory physiology","volume":"73","author":"Richardson","year":"2011","journal-title":"Annu. Rev. 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Genomics"},{"key":"2020060308400264000_ref16","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/gm554","article-title":"Copy number variants are a common cause of non-syndromic hearing loss","volume":"6","author":"Shearer","year":"2014","journal-title":"Genome Med."},{"key":"2020060308400264000_ref17","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1038\/gim.2015.89","article-title":"Comprehensive analysis via exome sequencing uncovers genetic etiology in autosomal recessive nonsyndromic deafness in a large multiethnic cohort","volume":"18","author":"Bademci","year":"2016","journal-title":"Genet. Med."},{"key":"2020060308400264000_ref18","first-page":"58","article-title":"Comprehensive genomic diagnosis of non-syndromic and syndromic hereditary hearing loss in Spanish patients","volume":"11","author":"Cabanillas","year":"2018","journal-title":"BMC Med. Genet."},{"key":"2020060308400264000_ref19","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s00439-018-1880-5","article-title":"Heterozygous missense variants of LMX1A lead to nonsyndromic hearing impairment and vestibular dysfunction","volume":"137","author":"Wesdorp","year":"2018","journal-title":"Hum. Genet."},{"key":"2020060308400264000_ref20","doi-asserted-by":"crossref","first-page":"e967","DOI":"10.1002\/mgg3.967","article-title":"Whole-exome sequencing identifies a donor splice-site variant in SMPX that causes rare X-linked congenital deafness","volume":"11","author":"Lv","year":"2019","journal-title":"Mol. Genet. Genomic. Med."},{"key":"2020060308400264000_ref21","doi-asserted-by":"crossref","first-page":"2286","DOI":"10.1002\/humu.23891","article-title":"Mutations in PLS1, encoding fimbrin, cause autosomal dominant non-syndromic hearing loss","volume":"40","author":"Morgan","year":"2019","journal-title":"Hum. Mutat."},{"key":"2020060308400264000_ref22","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1111\/j.1399-0004.2008.01130.x","article-title":"A novel autosomal dominant deafness locus (DFNA58) maps to 2p12-p21","volume":"75","author":"Lezirovitz","year":"2009","journal-title":"Clin. 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J. Hum. Genet."},{"key":"2020060308400264000_ref28","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/nature19057","article-title":"Analysis of protein-coding genetic variation in 60,706 humans","volume":"536","author":"Lek","year":"2016","journal-title":"Nature"},{"key":"2020060308400264000_ref29","doi-asserted-by":"crossref","first-page":"925","DOI":"10.4161\/rna.24604","article-title":"On the classification of long non-coding RNAs","volume":"10","author":"Ma","year":"2013","journal-title":"RNA Biol."},{"key":"2020060308400264000_ref30","first-page":"1","article-title":"Long non-coding RNAs in the regulation of gene expression: physiology and disease","volume":"5","author":"Fernandes","year":"2019","journal-title":"Noncoding RNA."},{"key":"2020060308400264000_ref31","doi-asserted-by":"crossref","first-page":"D313","DOI":"10.1093\/nar\/gkv1104","article-title":"BioGPS: building your own mash-up of gene annotations and expression profiles","volume":"44","author":"Wu","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"2020060308400264000_ref32","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1124\/mol.107.039263","article-title":"CB1 cannabinoid receptor activity is modulated by the cannabinoid receptor interacting protein CRIP 1a","volume":"72","author":"Niehaus","year":"2007","journal-title":"Mol. Pharmacol."},{"key":"2020060308400264000_ref33","doi-asserted-by":"crossref","first-page":"2767","DOI":"10.1093\/carcin\/bgt294","article-title":"Gene expression signature of non-involved lung tissue associated with survival in lung adenocarcinoma patients","volume":"34","author":"Galvan","year":"2013","journal-title":"Carcinogenesis"},{"key":"2020060308400264000_ref34","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.ajhg.2009.07.017","article-title":"Mutations in LOXHD1, an evolutionarily conserved stereociliary protein, disrupt hair cell function in mice and cause progressive hearing loss in humans","volume":"85","author":"Grillet","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"2020060308400264000_ref35","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1111\/j.1469-7793.2003.00525.x","article-title":"Membrane properties of type II spiral ganglion neurones identified in a neonatal rat cochlear slice","volume":"552","author":"Jagger","year":"2003","journal-title":"J. Physiol."},{"key":"2020060308400264000_ref36","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1016\/j.neuroscience.2009.05.036","article-title":"Quantitative analysis of the expression of the glutamate-aspartate transporter and identification of functional glutamate uptake reveal a role for cochlear fibrocytes in glutamate homeostasis","volume":"162","author":"Furness","year":"2009","journal-title":"Neuroscience"},{"key":"2020060308400264000_ref37","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1111\/cge.12683","article-title":"Genomic copy number alterations in non-syndromic hearing loss","volume":"89","author":"Rosenberg","year":"2016","journal-title":"Clin. Genet."},{"key":"2020060308400264000_ref38","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1159\/000342544","article-title":"Two new de novo interstitial duplications covering 2p14-p22.1: clinical and molecular analysis","volume":"139","author":"Kasnauskiene","year":"2012","journal-title":"Cytogenet. Genome Res."},{"key":"2020060308400264000_ref39","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1002\/ajmg.a.32293","article-title":"Consistent chromosome abnormalities identify novel polymicrogyria loci in 1p36.3, 2p16.1\u2013p23.1, 4q21.21\u2013q22.1, 6q26\u2013q27, and 21q2","volume":"146A","author":"Dobyns","year":"2008","journal-title":"Am. J. Med. Genet. A"},{"key":"2020060308400264000_ref40","doi-asserted-by":"crossref","first-page":"2892","DOI":"10.1002\/ajmg.a.33135","article-title":"Abnormal muscle development of the diaphragm in a fetus with 2p14\u2013p16 duplication","volume":"149A","author":"Guilherme","year":"2009","journal-title":"Am. J. Med. Genet. A"},{"key":"2020060308400264000_ref41","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1159\/000442747","article-title":"Hypercalcaemia in a patient with 2p13.2-p16.1 duplication","volume":"85","author":"Lodefalk","year":"2016","journal-title":"Horm. Res. Paediatr."},{"key":"2020060308400264000_ref42","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/j.ajhg.2019.04.004","article-title":"Expanding the boundaries of RNA sequencing as a diagnostic tool for rare Mendelian disease","volume":"104","author":"Gonorazky","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"2020060308400264000_ref43","doi-asserted-by":"crossref","first-page":"e1004942","DOI":"10.1371\/journal.pgen.1004942","article-title":"Aberrant gene expression in humans","volume":"11","author":"Zeng","year":"2015","journal-title":"PLoS Genet."},{"key":"2020060308400264000_ref44","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.ajhg.2015.12.023","article-title":"A burden of rare variants associated with extremes of gene expression in human peripheral blood","volume":"98","author":"Zhao","journal-title":"Am. J. Hum. Genet."},{"key":"2020060308400264000_ref45","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1038\/s41591-019-0457-8","article-title":"Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts","volume":"25","author":"Fr\u00e9sard","year":"2019","journal-title":"Nat. Med."},{"key":"2020060308400264000_ref46","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ajhg.2010.05.011","article-title":"Genomic duplication and overexpression of TJP2\/ZO-2 leads to altered expression of apoptosis genes in progressive nonsyndromic hearing loss DFNA51","volume":"87","author":"Walsh","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"2020060308400264000_ref47","doi-asserted-by":"crossref","first-page":"e1002309","DOI":"10.1371\/journal.pgen.1002309","article-title":"Cell type-specific transcriptome analysis reveals a major role for Zeb1 and miR-200b in mouse inner ear morphogenesis","volume":"7","author":"Hertzano","year":"2011","journal-title":"PLoS Genet."},{"key":"2020060308400264000_ref48","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.heares.2015.08.013","article-title":"A comprehensive catalogue of the coding and non-coding transcripts of the human inner ear","volume":"333","author":"Schrauwen","year":"2016","journal-title":"Hear. Res."},{"key":"2020060308400264000_ref49","doi-asserted-by":"crossref","first-page":"3691","DOI":"10.1038\/s41467-018-06033-3","article-title":"Neuronal heterogeneity and stereotyped connectivity in the auditory afferent system","volume":"9","author":"Petitpr\u00e9","year":"2018","journal-title":"Nat. Commun."},{"key":"2020060308400264000_ref50","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1016\/j.cell.2018.07.008","article-title":"Hair cell Mechanotransduction regulates spontaneous activity and spiral ganglion subtype specification in the auditory system","volume":"174","author":"Sun","year":"2018","journal-title":"Cell"},{"key":"2020060308400264000_ref51","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1111\/cge.12915","article-title":"Extension of the clinical and molecular phenotype of DIAPH1-associated autosomal dominant hearing loss (DFNA1)","volume":"91","author":"Neuhaus","year":"2017","journal-title":"Clin. Genet."},{"key":"2020060308400264000_ref52","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1172\/JCI97350","article-title":"Modifier variant of METTL13 suppresses human GAB1-associated profound deafness","volume":"128","author":"Yousaf","year":"2018","journal-title":"J. Clin. Invest."},{"key":"2020060308400264000_ref53","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1111\/jnc.14021","article-title":"CRIP1a inhibits endocytosis of G-protein coupled receptors activated by endocannabinoids and glutamate by a common molecular mechanism","volume":"141","author":"Mascia","year":"2017","journal-title":"J. Neurochem."},{"key":"2020060308400264000_ref54","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1007\/s00429-015-1027-6","article-title":"Cannabinoid receptor-interacting protein Crip1a modulates CB1 receptor signaling in mouse hippocampus","volume":"22","author":"Guggenhuber","year":"2016","journal-title":"Brain Struct. Funct."},{"key":"2020060308400264000_ref55","doi-asserted-by":"crossref","first-page":"RC174","DOI":"10.1523\/JNEUROSCI.21-20-j0005.2001","article-title":"Cerebellar depolarization-induced suppression of inhibition is mediated by endogenous cannabinoids","volume":"21","author":"Kreitzer","year":"2001","journal-title":"J. Neurosci."},{"key":"2020060308400264000_ref56","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/S0896-6273(03)00476-8","article-title":"Neocortical LTD via coincident activation of presynaptic NMDA and cannabinoid receptors","volume":"39","author":"Sj\u00f6str\u00f6m","year":"2003","journal-title":"Neuron"},{"key":"2020060308400264000_ref57","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1038\/35069076","article-title":"Endogenous cannabinoids mediate retrograde signaling at hippocampal synapses","volume":"410","author":"Wilson","year":"2001","journal-title":"Nature"},{"key":"2020060308400264000_ref58","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1124\/mol.114.096495","article-title":"Cannabinoid receptor-interacting protein 1a modulates CB1 receptor signaling and regulation","volume":"87","author":"Smith","year":"2015","journal-title":"Mol. Pharmacol."},{"key":"2020060308400264000_ref59","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/j.cellsig.2014.11.006","article-title":"Cannabinoid receptor interacting protein (CRIP1a) attenuates CB1R signaling in neuronal cells","volume":"27","author":"Blume","year":"2015","journal-title":"Cell. Signal."},{"key":"2020060308400264000_ref60","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.5114\/aoms.2017.65829","article-title":"Value of CNRIP1 promoter methylation in colorectal cancer screening and prognosis assessment and its influence on the activity of cancer cells","volume":"13","author":"Zhang","year":"2017","journal-title":"Arch. Med. Sci."},{"key":"2020060308400264000_ref61","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/1476-4598-10-85","article-title":"Identification of an epigenetic biomarker panel with high sensitivity and specificity for colorectal cancer and adenomas","volume":"10","author":"Lind","year":"2011","journal-title":"Mol. Cancer"},{"key":"2020060308400264000_ref62","doi-asserted-by":"crossref","first-page":"2855","DOI":"10.1002\/ijc.25951","article-title":"Identification and validation of highly frequent CpG island hypermethylation in colorectal adenomas and carcinomas","volume":"129","author":"Oster","year":"2011","journal-title":"Int. J. Cancer"},{"key":"2020060308400264000_ref63","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1002\/jms.4032","article-title":"Screening of exon methylation biomarkers for colorectal cancer via LC-MS\/MS strategy","volume":"52","author":"Huang","year":"2017","journal-title":"J. Mass Spectrom."},{"key":"2020060308400264000_ref64","doi-asserted-by":"crossref","first-page":"2535","DOI":"10.3892\/or.2014.3133","article-title":"DNA methylation status of a distinctively different subset of genes is associated with each histologic Lauren classification subtype in early gastric carcinogenesis","volume":"31","author":"Chong","year":"2014","journal-title":"Oncol. Rep."},{"key":"2020060308400264000_ref65","doi-asserted-by":"crossref","first-page":"428","DOI":"10.4161\/epi.27554","article-title":"Colorectal cancer DNA methylation marker panel validated with high performance in non-Hodgkin lymphoma","volume":"9","author":"Bethge","year":"2014","journal-title":"Epigenetics"},{"key":"2020060308400264000_ref66","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1002\/hep.27707","article-title":"Four DNA methylation biomarkers in biliary brush samples accurately identify the presence of cholangiocarcinoma","volume":"61","author":"Andresen","year":"2015","journal-title":"Hepatology"},{"key":"2020060308400264000_ref67","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1111\/j.1365-2141.1990.tb02565.x","article-title":"P47 phosphoprotein of blood platelets (pleckstrin) is a major target for phorbol ester-induced protein phosphorylation in intact platelets, granulocytes, lymphocytes, monocytes and cultured leukaemic cells: absence of P47 in non-haematopoietic cells","volume":"74","author":"Gailani","year":"1990","journal-title":"Br. J. Haematol."},{"key":"2020060308400264000_ref68","doi-asserted-by":"crossref","first-page":"3577","DOI":"10.1182\/blood-2008-09-178913","article-title":"Loss of pleckstrin defines a novel pathway for PKC-mediated exocytosis","volume":"113","author":"Lian","year":"2009","journal-title":"Blood"},{"key":"2020060308400264000_ref69","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1083\/jcb.136.5.1071","article-title":"Pleckstrin associates with plasma membranes and induces the formation of membrane projections: requirements for phosphorylation and the NH2-terminal PH domain","volume":"136","author":"Ma","year":"1997","journal-title":"J. Cell Biol."},{"key":"2020060308400264000_ref70","doi-asserted-by":"crossref","first-page":"28730","DOI":"10.1074\/jbc.274.40.28730","article-title":"Pleckstrin induces cytoskeletal reorganization via a Rac-dependent pathway","volume":"274","author":"Ma","year":"1999","journal-title":"J. Biol. Chem."},{"key":"2020060308400264000_ref71","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1083\/jcb.150.6.1461","article-title":"Phosphorylated pleckstrin induces cell spreading via an integrin-dependent pathway","volume":"150","author":"Roll","year":"2000","journal-title":"J. Cell Biol."},{"key":"2020060308400264000_ref72","doi-asserted-by":"crossref","first-page":"4254","DOI":"10.1002\/pmic.200900060","article-title":"Proteomic identification of pleckstrin-associated proteins in platelets: possible interactions with actin","volume":"9","author":"Baig","year":"2009","journal-title":"Proteomics"},{"key":"2020060308400264000_ref73","doi-asserted-by":"crossref","first-page":"21515","DOI":"10.1074\/jbc.274.31.21515","article-title":"Pleckstrin 2, a widely expressed paralog of pleckstrin involved in actin rearrangement","volume":"274","author":"Hu","year":"1999","journal-title":"J. Biol. Chem."},{"key":"2020060308400264000_ref74","doi-asserted-by":"crossref","first-page":"647","DOI":"10.4049\/jimmunol.179.1.647","article-title":"Phosphorylation of pleckstrin increases proinflammatory cytokine secretion by mononuclear phagocytes in diabetes mellitus","volume":"179","author":"Ding","year":"2007","journal-title":"J. Immunol."},{"key":"2020060308400264000_ref75","doi-asserted-by":"crossref","first-page":"18475","DOI":"10.1038\/srep18475","article-title":"Transcriptome analysis reveals mucin 4 to be highly associated with periodontitis and identifies pleckstrin as a link to systemic diseases","volume":"5","author":"Lundmark","year":"2015","journal-title":"Sci. Rep."},{"key":"2020060308400264000_ref76","doi-asserted-by":"crossref","first-page":"685","DOI":"10.2174\/157015911798376316","article-title":"A role for Calcineurin in Alzheimer\u2019s disease","volume":"9","author":"Reese","year":"2011","journal-title":"Curr. Neuropharmacol."},{"key":"2020060308400264000_ref77","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1016\/S0091-6749(95)70202-4","article-title":"The role of calcineurin in immune system responses","volume":"96","author":"Kincaid","year":"1995","journal-title":"J. Allergy Clin. Immunol."},{"key":"2020060308400264000_ref78","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/S0272-6386(97)90100-1","article-title":"Expression and function of calcineurin in the mammalian nephron: physiological roles, receptor signaling, and ion transport","volume":"30","author":"Tumlin","year":"1997","journal-title":"Am. J. Kidney Dis."},{"key":"2020060308400264000_ref79","doi-asserted-by":"crossref","first-page":"34450","DOI":"10.1074\/jbc.274.48.34450","article-title":"High level calcineurin activity predisposes neuronal cells to apoptosis","volume":"274","author":"Asai","year":"1999","journal-title":"J. Biol. Chem."},{"key":"2020060308400264000_ref80","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1152\/physrev.2000.80.4.1483","article-title":"Calcineurin: form and function","volume":"80","author":"Rusnak","year":"2000","journal-title":"Physiol. Rev."},{"key":"2020060308400264000_ref81","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.jalz.2013.02.010","article-title":"Variants in PPP3R1 and MAPT are associated with more rapid functional decline in Alzheimer's disease: the Cache County dementia progression study","volume":"10","author":"Peterson","year":"2014","journal-title":"Alzheimers Dement."},{"key":"2020060308400264000_ref82","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.intimp.2018.10.038","article-title":"The calcineurin regulatory subunit polymorphism and the treatment efficacy of tacrolimus for idiopathic membranous nephropathy","volume":"65","author":"Zhu","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"2020060308400264000_ref83","doi-asserted-by":"crossref","first-page":"6417","DOI":"10.1074\/jbc.275.9.6417","article-title":"Calcineurin is downstream of the inositol 1,4,5-trisphosphate receptor in the apoptotic and cell growth pathways","volume":"275","author":"Jayaraman","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2020060308400264000_ref84","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1038\/nrm1150","article-title":"Regulation of cell death: the calcium-apoptotic link","volume":"4","author":"Orrenius","year":"2003","journal-title":"Nat. Rev. Cell. Biol."},{"key":"2020060308400264000_ref85","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1002\/jnr.20267","article-title":"Calcineurin activation contributes to noise-induced hearing loss","volume":"78","author":"Minami","year":"2004","journal-title":"J. Neurosci. Res."},{"key":"2020060308400264000_ref86","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1038\/nrg3074","article-title":"Non-coding RNAs in human disease","volume":"12","author":"Esteller","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"2020060308400264000_ref87","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1038\/nature08975","article-title":"Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis","volume":"464","author":"Gupta","year":"2010","journal-title":"Nature"},{"key":"2020060308400264000_ref88","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.cell.2010.06.040","article-title":"A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response","volume":"142","author":"Huarte","year":"2010","journal-title":"Cell"},{"key":"2020060308400264000_ref89","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/nature10398","article-title":"lincRNAs act in the circuitry controlling pluripotency and differentiation","volume":"477","author":"Guttma","year":"2011","journal-title":"Nature"},{"key":"2020060308400264000_ref90","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.cell.2013.06.020","article-title":"lincRNAs: genomics, evolution, and mechanisms","volume":"154","author":"Ulitsky","year":"2013","journal-title":"Cell"},{"key":"2020060308400264000_ref91","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1101\/gr.132159.111","article-title":"The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression","volume":"22","author":"Derrien","year":"2012","journal-title":"Genome Res."},{"key":"2020060308400264000_ref92","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.cell.2018.01.011","article-title":"Functional classification and experimental dissection of long noncoding RNAs","volume":"172","author":"Kopp","year":"2018","journal-title":"Cell"},{"key":"2020060308400264000_ref93","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/ng.806","article-title":"A framework for variation discovery and genotyping using next-generation DNA sequencing data","volume":"43","author":"DePristo","year":"2011","journal-title":"Nat. Genet."},{"key":"2020060308400264000_ref94","doi-asserted-by":"crossref","first-page":"2865","DOI":"10.1093\/bioinformatics\/btp394","article-title":"Pindel: a pattern growth approach to detect break points of large deletions and medium sized insertions from paired-end short reads","volume":"25","author":"Ye","year":"2009","journal-title":"Bioinformatics"},{"key":"2020060308400264000_ref95","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: functional annotation of genetic variants from next-generation sequencing data","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"2020060308400264000_ref96","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4161\/fly.19695","article-title":"A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3","volume":"6","author":"Cingolani","year":"2012","journal-title":"Fly (Austin)"},{"key":"2020060308400264000_ref97","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1002\/humu.23220","article-title":"Exomic variants of an elderly cohort of Brazilians in the ABraOM database","volume":"38","author":"Naslavsky","year":"2017","journal-title":"Hum. Mutat."},{"key":"2020060308400264000_ref98","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.ajhg.2011.05.017","article-title":"Using VAAST to identify an X-linked disorder resulting in lethality in male infants due to N-terminal Acetyltransferase deficiency","volume":"89","author":"Rope","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"2020060308400264000_ref99","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations","volume":"7","author":"Adzhubei","year":"2010","journal-title":"Nat. Methods"},{"key":"2020060308400264000_ref100","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(\u2212Delta DeltaC(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"2020060308400264000_ref101","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1159\/000109731","article-title":"Multilocus lod scores in large pedigrees: combination of exact and approximate calculations","volume":"65","author":"Tong","year":"2008","journal-title":"Hum. Hered."},{"key":"2020060308400264000_ref102","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1186\/1471-2105-13-134","article-title":"Primer-BLAST: a tool to design target-specific primers for polymerase chain reaction","volume":"13","author":"Ye","year":"2012","journal-title":"BMC Bioinf."},{"key":"2020060308400264000_ref103","doi-asserted-by":"crossref","first-page":"3848","DOI":"10.1002\/cne.22429","article-title":"Architecture of cannabinoid signaling in mouse retina","volume":"518","author":"Hu","year":"2010","journal-title":"J. Comp. 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