{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:08:36Z","timestamp":1780445316049,"version":"3.54.1"},"reference-count":19,"publisher":"BMJ","issue":"5","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2015,4,10]]},"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Aetiological assessment of 71 probands whose clinical presentation suggested a genetic syndrome or auditory neuropathy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Sanger sequencing was performed on DNA isolated from peripheral blood or lymphoblastoid cell lines. Genes were selected for sequencing based on each patient's clinical presentation and suspected diagnosis. Observed DNA sequence variations were assessed for pathogenicity by review of the scientific literature, and mutation and polymorphism databases, through the use of in silico tools including sorting intolerant from tolerant (SIFT) and polymorphism phenotyping (PolyPhen), and according to the recommendations of the American College of Medical Genetics and Genomics for the interpretation of DNA sequence variations. Novel DNA sequence variations were sought in controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>DNA sequencing of the coding and near-coding regions of genes relevant to each patient's clinical presentation revealed 37 sequence variations of known or uncertain pathogenicity in 9 genes from 25 patients. 14 novel sequence variations were discovered. Assessment of phenotypes revealed notable findings in 9 patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>DNA sequencing in patients whose clinical presentation suggested a genetic syndrome or auditory neuropathy provided opportunities for aetiological assessment and more precise genetic counselling of patients and families. The failure to identify a genetic aetiology in many patients in this study highlights the extreme heterogeneity of genetic hearing loss, the incompleteness of current knowledge of aetiologies of hearing loss, and the limitations of conventional DNA sequencing strategies that evaluate only coding and near-coding segments of genes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2014-007506","type":"journal-article","created":{"date-parts":[[2015,5,19]],"date-time":"2015-05-19T21:21:05Z","timestamp":1432070465000},"page":"e007506","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["DNA sequence analysis and genotype\u2013phenotype assessment in 71 patients with syndromic hearing loss or auditory neuropathy"],"prefix":"10.1136","volume":"5","author":[{"given":"Hsiao-Yuan","family":"Tang","sequence":"first","affiliation":[{"name":"Bobby R Alford Department of Otolaryngology\u2014Head and Neck Surgery, Baylor College of Medicine, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Fang","sequence":"additional","affiliation":[{"name":"Medical Genetics Laboratories, Baylor College of Medicine, Houston, Texas, USA"},{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry W","family":"Lin","sequence":"additional","affiliation":[{"name":"Bobby R Alford Department of Otolaryngology\u2014Head and Neck Surgery, Baylor College of Medicine, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Darilek","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooke T","family":"Osborne","sequence":"additional","affiliation":[{"name":"Bobby R Alford Department of Otolaryngology\u2014Head and Neck Surgery, Baylor College of Medicine, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo Ann","family":"Haymond","sequence":"additional","affiliation":[{"name":"Bobby R Alford Department of Otolaryngology\u2014Head and Neck Surgery, Baylor College of Medicine, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spiros","family":"Manolidis","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head & Neck Surgery, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin B","family":"Roa","sequence":"additional","affiliation":[{"name":"Myriad Genetic Laboratories, Salt Lake City, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S","family":"Oghalai","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, Stanford University, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raye L","family":"Alford","sequence":"additional","affiliation":[{"name":"Bobby R Alford Department of Otolaryngology\u2014Head and Neck Surgery, Baylor College of Medicine, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2015,5,19]]},"reference":[{"key":"2025121408510905000_5.5.e007506.1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1101\/gr.9.1.7","article-title":"Genomics and hearing impairment","volume":"9","author":"Keats","year":"1999","journal-title":"Genome Res"},{"key":"2025121408510905000_5.5.e007506.2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.35.102401.091224"},{"key":"2025121408510905000_5.5.e007506.3","unstructured":"Toriello H , Smith S . Hereditary hearing loss and its syndromes. 3rd edn. New York: Oxford University Press, 2013."},{"key":"2025121408510905000_5.5.e007506.4","unstructured":"Van Camp G , Smith RJH . Hereditary hearing loss homepage. http:\/\/dnalab-www.uia.ac.be\/dnalab\/hhh\/; http:\/\/hereditaryhearingloss.org\/ (accessed 19 Mar 2015)."},{"key":"2025121408510905000_5.5.e007506.5","unstructured":"Smith RJH , Gurrola JG II , Kelley PM . OTOF-Related deafness. 29 Feb 2008 [Updated 14 Jun 2011]. In: Pagon RA, Adam MP, Ardinger HH, et al, eds. GeneReviews\u00ae. 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