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Tinnitus phenotyping included audiological (standard and high-frequency audiometry, Auditory Brainstem Responses (ABR) and Auditory Middle Latency Responses (AMLR)), psychoacoustic and psychometric assessment by a Visual Analog Scale (VAS) for tinnitus annoyance, the Tinnitus Handicap Inventory (THI), the test on Hypersensitivity to Sound (THS-G\u00dcF), the Patient Health Questionnaire (PHQ-9), the Hospital Anxiety and Depression Scale (HADS) and the Montreal Cognitive Assessment (MoCA).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>All patients reported a persistent, unilateral noise-type tinnitus, mainly described as white noise or narrowband noise. Seven patients (58%) were considered to have extreme phenotype (THI score\u2009&gt;\u200976), and all patients reported some degree of hyperacusis (THS-G\u00dcF score\u2009&gt;\u200918 in 75% of patients). Seven patients scored MoCA\u2009&lt;\u200926, regardless of the age reported, suggesting a mild cognitive disorder. ABR showed no significant differences in latencies and amplitudes between ears with or without tinnitus. Similarly, the latencies of Pa, Pb waves, and NaPa complex in the AMLR did not differ based on the presence of tinnitus. However, there were statistical differences in the amplitudes of Pa waves in AMLR, with significantly greater amplitudes observed in ears with tinnitus.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Patients with <jats:italic>ANK2<\/jats:italic> variants and severe tinnitus exhibit an endophenotype featuring hyperacusis, persistent noise-like tinnitus, high-frequency hearing loss, and decreased amplitudes in AMLR. However, anxiety, depression, and cognitive symptoms vary among individuals.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00405-024-08561-9","type":"journal-article","created":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T06:02:28Z","timestamp":1710914548000},"page":"4071-4080","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Phenotypic spectrum of tinnitus patients bearing rare ANK2 gene variants"],"prefix":"10.1007","volume":"281","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5505-8734","authenticated-orcid":false,"given":"Juan","family":"Martin-Lagos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8609-5356","authenticated-orcid":false,"given":"Alberto","family":"Bernal-Robledano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2722-4947","authenticated-orcid":false,"given":"Patricia","family":"Perez-Carpena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2506-1120","authenticated-orcid":false,"given":"Mar","family":"Lamolda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1027-8594","authenticated-orcid":false,"given":"Alba","family":"Escalera-Balsera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6104-0941","authenticated-orcid":false,"given":"Lidia","family":"Frejo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8583-1430","authenticated-orcid":false,"given":"Jose A.","family":"Lopez-Escamez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,20]]},"reference":[{"key":"8561_CR1","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1016\/j.amjmed.2010.02.015","volume":"123","author":"J Shargorodsky","year":"2010","unstructured":"Shargorodsky J, Curhan GC, Farwell WR (2010) Prevalence and characteristics of tinnitus among US adults. 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