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The majority of cases are considered sporadic, although familial aggregation has been recognized in European and Korean populations, and the search for familial MD genes has been elusive until the last few years. Detailed phenotyping and cluster analyses have found several clinical predictors for different subgroups of patients, which may indicate different mechanisms, including genetic and immune factors. The genes associated with familial MD are<ns4:italic>COCH<\/ns4:italic>,<ns4:italic>FAM136A<\/ns4:italic>,<ns4:italic>DTNA<\/ns4:italic>,<ns4:italic>PRKCB<\/ns4:italic>,<ns4:italic>SEMA3D<\/ns4:italic>, and<ns4:italic>DPT<\/ns4:italic>. At least two mechanisms have been involved in MD: (a) a pro-inflammatory immune response mediated by interleukin-1 beta (IL-1\u03b2), tumor necrosis factor alpha (TNF\u03b1), and IL-6, and (b) a nuclear factor-kappa B (NF-\u03baB)-mediated inflammation in the carriers of the single-nucleotide variant rs4947296. It is conceivable that microbial antigens trigger inflammation with release of pro-inflammatory cytokines at different sites within the cochlea, such as the endolymphatic sac, the stria vascularis, or the spiral ligament, leading to fluid imbalance with an accumulation of endolymph. Computational integration of clinical and \u201comics\u201d data eventually should transform the management of MD from \u201cone pill fits all\u201d to precise patient stratification and a personalized approach. This article lays out a proposal for an algorithm for the genetic diagnosis of MD. This approach will facilitate the identification of new molecular targets for individualized treatment, including immunosuppressant and gene therapy, in the near future.<\/ns4:p>","DOI":"10.12688\/f1000research.14417.1","type":"journal-article","created":{"date-parts":[[2018,8,15]],"date-time":"2018-08-15T08:55:06Z","timestamp":1534323306000},"page":"1295","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":42,"title":["Towards personalized medicine in M\u00e9ni\u00e8re\u2019s disease"],"prefix":"10.12688","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8583-1430","authenticated-orcid":false,"given":"Jose 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Lopez-Escamez is supported by the Luxembourg National Research Fund (grant INTER\/Mobility\/17\/11772209), M\u00e9ni\u00e8re\u2019s Society (UK), Instituto de Salud Carlos III (grant PI17\/01644), and FEDER Funds and H2020 Marie Sk\u0142odowska-Curie Actions (ITN-2016\u2013722046) from the EU. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":3,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}