{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T23:40:44Z","timestamp":1782258044754,"version":"3.54.5"},"reference-count":16,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,3,30]],"date-time":"2020-03-30T00:00:00Z","timestamp":1585526400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Deafness and hearing loss are common conditions that can be seen independently or as part of a syndrome and are often mediated by genetic causes. We sought to develop and validate a hereditary hearing loss panel (HHLP) to detect single nucleotide variants (SNVs), insertions and deletions (indels), and copy number variants (CNVs) in 166 genes related to nonsyndromic and syndromic hearing loss.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We developed a custom-capture next-generation sequencing (NGS) reagent to detect all coding regions, \u00b110 flanking bp, for the 166 genes related to nonsyndromic and syndromic hearing loss. Our validation consisted of testing 52 samples to establish accuracy, reproducibility, and analytical sensitivity. In addition to NGS, supplementary methods, including multiplex ligation-dependent probe amplification, long-range PCR, and Sanger sequencing, were used to ensure coverage of regions that had high complexity or homology.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We observed 100% positive and negative percentage agreement for detection of SNVs (n\u2009=\u2009362), small indels (1\u201322\u2009bp, n\u2009=\u200925), and CNVs (gains, n\u2009=\u20098; losses, n\u2009=\u200917). Finally, we showed that this assay was able to detect variants with a variant allele frequency \u226520% for SNVs and indels and \u226530% to 35% for CNVs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We validated an HHLP that detects SNVs, indels, and CNVs in 166 genes related to syndromic and nonsyndromic hearing loss. The results of this assay can be utilized to confirm a diagnosis of hearing loss and related syndromic disorders associated with known causal genes.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jalm\/jfaa021","type":"journal-article","created":{"date-parts":[[2020,2,3]],"date-time":"2020-02-03T20:09:25Z","timestamp":1580760565000},"page":"467-479","source":"Crossref","is-referenced-by-count":6,"title":["Development and Validation of a Next-Generation Sequencing Panel for Syndromic and Nonsyndromic Hearing Loss"],"prefix":"10.1093","volume":"5","author":[{"given":"Malinda","family":"Butz","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Genomics Laboratory, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber","family":"McDonald","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Genomics Laboratory, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick A","family":"Lundquist","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Genomics Laboratory, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Meyer","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Genomics Laboratory, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Harrington","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Genomics Laboratory, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Kester","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Genomics Laboratory, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam I","family":"Stein","sequence":"first","affiliation":[{"name":"Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nipun A","family":"Mistry","sequence":"first","affiliation":[{"name":"Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Zimmerman Zuckerman","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Clinical Genome Sequencing Laboratory, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyv","family":"Niu","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Genomics Laboratory, Mayo Clinic, Rochester, MN"},{"name":"Department of Laboratory Medicine and Pathology, Clinical Genome Sequencing Laboratory, Mayo Clinic, Rochester, MN"},{"name":"Department of Clinical Genomics, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Schimmenti","sequence":"first","affiliation":[{"name":"Department of Clinical Genomics, Mayo Clinic, Rochester, MN"},{"name":"Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, MN"},{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Hasadsri","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Genomics Laboratory, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole J","family":"Boczek","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Genomics Laboratory, Mayo Clinic, Rochester, MN"},{"name":"Department of Clinical Genomics, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,3,30]]},"reference":[{"key":"2020043015585671700_jfaa021-B1","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1056\/NEJMra050700","article-title":"Newborn hearing screening\u2014a silent revolution","volume":"354","author":"Morton","year":"2006","journal-title":"N Engl J Med"},{"key":"2020043015585671700_jfaa021-B2","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/gim.2014.2","article-title":"American College of Medical Genetics and Genomics guideline for the clinical evaluation and etiologic diagnosis of hearing loss","volume":"16","author":"Alford","year":"2014","journal-title":"Genet Med"},{"key":"2020043015585671700_jfaa021-B3","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1097\/01.GIM.0000144187.21727.28","article-title":"Genetic testing as part of the early hearing detection and intervention (EHDI) process","volume":"6","author":"Schimmenti","year":"2004","journal-title":"Genet Med"},{"key":"2020043015585671700_jfaa021-B4","article-title":"ClinGen expert clinical validity curation of 164 hearing loss gene\u2013disease pairs","volume":"21","author":"DiStefano","year":"2019","journal-title":"Genet Med"},{"key":"2020043015585671700_jfaa021-B5","doi-asserted-by":"crossref","first-page":"16094","DOI":"10.1038\/nrdp.2016.94","article-title":"Congenital hearing loss","volume":"3","author":"Korver","year":"2017","journal-title":"Nat Rev Dis Primers"},{"key":"2020043015585671700_jfaa021-B6","author":"Lentz","year":"1999"},{"key":"2020043015585671700_jfaa021-B7","author":"Tranebj\u00e6rg","year":"2002"},{"key":"2020043015585671700_jfaa021-B8","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1038\/s41467-017-00595-4","article-title":"A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction","volume":"8","author":"Bowl","year":"2017","journal-title":"Nat Commun"},{"key":"2020043015585671700_jfaa021-B9","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1097\/MOP.0000000000000410","article-title":"Navigating genetic diagnostics in patients with hearing loss","volume":"28","author":"Sloan-Heggen","year":"2016","journal-title":"Curr Opin Pediatr"},{"key":"2020043015585671700_jfaa021-B10","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"2020043015585671700_jfaa021-B11","doi-asserted-by":"crossref","first-page":"2678","DOI":"10.1093\/bioinformatics\/btu363","article-title":"PatternCNV: a versatile tool for detecting copy number changes from exome sequencing data","volume":"30","author":"Wang","year":"2014","journal-title":"Bioinformatics"},{"key":"2020043015585671700_jfaa021-B12","author":"Usami","year":"2004"},{"key":"2020043015585671700_jfaa021-B13","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.jmoldx.2017.05.011","article-title":"A droplet digital PCR method for severe combined immunodeficiency newborn screening","volume":"19","author":"Vidal-Folch","year":"2017","journal-title":"J Mol Diagn"},{"key":"2020043015585671700_jfaa021-B14","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":"2020043015585671700_jfaa021-B15","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1002\/humu.23630","article-title":"Expert specification of the ACMG\/AMP variant interpretation guidelines for genetic hearing loss","volume":"39","author":"Oza","year":"2018","journal-title":"Hum Mutat"},{"key":"2020043015585671700_jfaa021-B16","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1056\/NEJMsr1406261","article-title":"ClinGen\u2014the clinical genome resource","volume":"372","author":"Rehm","year":"2015","journal-title":"N Engl J Med"}],"container-title":["The Journal of Applied Laboratory Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jalm\/article-pdf\/5\/3\/467\/33150000\/jfaa021.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jalm\/article-pdf\/5\/3\/467\/33150000\/jfaa021.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,4,30]],"date-time":"2020-04-30T19:59:11Z","timestamp":1588276751000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jalm\/article\/5\/3\/467\/5813833"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,30]]},"references-count":16,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,3,30]]},"published-print":{"date-parts":[[2020,5,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jalm\/jfaa021","relation":{},"ISSN":["2576-9456","2475-7241"],"issn-type":[{"value":"2576-9456","type":"print"},{"value":"2475-7241","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,5]]},"published":{"date-parts":[[2020,3,30]]}}}