{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T20:11:15Z","timestamp":1793045475324,"version":"4.5.0"},"reference-count":71,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"20","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[1998,5,26]]},"abstract":"<jats:p>\n            <jats:italic>Background<\/jats:italic>\n            \u2014Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disease of unknown etiology that causes arrhythmias, heart failure, and sudden death. Diagnosis can be difficult, and this hampers investigation of its molecular basis. Forms of ARVC in which gene penetrance and disease expression are greater should facilitate genetic study. We undertook a clinical and genetic investigation of Naxos disease, originally described by Protonotarios in 1986. This disease constitutes the triad of ARVC, diffuse nonepidermolytic palmoplantar keratoderma, and woolly hair.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods and Results<\/jats:italic>\n            \u2014We evaluated the population of Naxos, Greece, to identify probands, which was followed by family screening. Twenty-one affected persons from 9 families of 150 persons were identified. Linkage analysis was performed with microsatellite markers. The disease locus mapped to 17q21. A peak 2-point LOD score of 3.62 at \u03b8=0.0 was found with a marker within intron 4 of the keratin 9 gene, a member of the type I (acidic) keratin family. A preserved homozygous disease haplotype was identified. Haplotype analysis delimited the disease interval.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            \u2014Hair and skin abnormalities were found to be reliable markers of subsequent heart disease. This suggests the presence of a single mutant gene with novel cardiac, skin, and hair function or two or more tightly linked disease genes. Recessive inheritance of Naxos disease and a founder effect were demonstrated. Identification of a fully informative genetic marker linked to the disease and uncommon in the background population may be of use as a test to identify disease gene carriers.\n          <\/jats:p>","DOI":"10.1161\/01.cir.97.20.2049","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:41:02Z","timestamp":1339461662000},"page":"2049-2058","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":189,"title":["Gene for Arrhythmogenic Right Ventricular Cardiomyopathy With Diffuse Nonepidermolytic Palmoplantar Keratoderma and Woolly Hair (Naxos Disease) Maps to 17q21"],"prefix":"10.1161","volume":"97","author":[{"given":"Aman S.","family":"Coonar","sequence":"first","affiliation":[{"name":"From the Departments of Cardiological Sciences (A.S.C., E.W.A.N., R.K.M., W.J.M.), Dermatology (S.C.), Pathology (M.I.O.), and Medical Genetics (V.A.M.), St George\u2019s Hospital Medical School, London, UK; Yannis Protonotarios Medical Center, Hora Naxos, Naxos, Greece (N.P., A.T.); and Genetics Team, Section of Epidemiology, Institute of Cancer Research, Royal Marsden Hospital, Sutton, Surrey, UK (R.S.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikos","family":"Protonotarios","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiological Sciences (A.S.C., E.W.A.N., R.K.M., W.J.M.), Dermatology (S.C.), Pathology (M.I.O.), and Medical Genetics (V.A.M.), St George\u2019s Hospital Medical School, London, UK; Yannis Protonotarios Medical Center, Hora Naxos, Naxos, Greece (N.P., A.T.); and Genetics Team, Section of Epidemiology, Institute of Cancer Research, Royal Marsden Hospital, Sutton, Surrey, UK (R.S.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adalena","family":"Tsatsopoulou","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiological Sciences (A.S.C., E.W.A.N., R.K.M., W.J.M.), Dermatology (S.C.), Pathology (M.I.O.), and Medical Genetics (V.A.M.), St George\u2019s Hospital Medical School, London, UK; Yannis Protonotarios Medical Center, Hora Naxos, Naxos, Greece (N.P., A.T.); and Genetics Team, Section of Epidemiology, Institute of Cancer Research, Royal Marsden Hospital, Sutton, Surrey, UK (R.S.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward W.A.","family":"Needham","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiological Sciences (A.S.C., E.W.A.N., R.K.M., W.J.M.), Dermatology (S.C.), Pathology (M.I.O.), and Medical Genetics (V.A.M.), St George\u2019s Hospital Medical School, London, UK; Yannis Protonotarios Medical Center, Hora Naxos, Naxos, Greece (N.P., A.T.); and Genetics Team, Section of Epidemiology, Institute of Cancer Research, Royal Marsden Hospital, Sutton, Surrey, UK (R.S.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard S.","family":"Houlston","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiological Sciences (A.S.C., E.W.A.N., R.K.M., W.J.M.), Dermatology (S.C.), Pathology (M.I.O.), and Medical Genetics (V.A.M.), St George\u2019s Hospital Medical School, London, UK; Yannis Protonotarios Medical Center, Hora Naxos, Naxos, Greece (N.P., A.T.); and Genetics Team, Section of Epidemiology, Institute of Cancer Research, Royal Marsden Hospital, Sutton, Surrey, UK (R.S.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep","family":"Cliff","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiological Sciences (A.S.C., E.W.A.N., R.K.M., W.J.M.), Dermatology (S.C.), Pathology (M.I.O.), and Medical Genetics (V.A.M.), St George\u2019s Hospital Medical School, London, UK; Yannis Protonotarios Medical Center, Hora Naxos, Naxos, Greece (N.P., A.T.); and Genetics Team, Section of Epidemiology, Institute of Cancer Research, Royal Marsden Hospital, Sutton, Surrey, UK (R.S.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark I.","family":"Otter","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiological Sciences (A.S.C., E.W.A.N., R.K.M., W.J.M.), Dermatology (S.C.), Pathology (M.I.O.), and Medical Genetics (V.A.M.), St George\u2019s Hospital Medical School, London, UK; Yannis Protonotarios Medical Center, Hora Naxos, Naxos, Greece (N.P., A.T.); and Genetics Team, Section of Epidemiology, Institute of Cancer Research, Royal Marsden Hospital, Sutton, Surrey, UK (R.S.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria A.","family":"Murday","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiological Sciences (A.S.C., E.W.A.N., R.K.M., W.J.M.), Dermatology (S.C.), Pathology (M.I.O.), and Medical Genetics (V.A.M.), St George\u2019s Hospital Medical School, London, UK; Yannis Protonotarios Medical Center, Hora Naxos, Naxos, Greece (N.P., A.T.); and Genetics Team, Section of Epidemiology, Institute of Cancer Research, Royal Marsden Hospital, Sutton, Surrey, UK (R.S.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raj K.","family":"Mattu","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiological Sciences (A.S.C., E.W.A.N., R.K.M., W.J.M.), Dermatology (S.C.), Pathology (M.I.O.), and Medical Genetics (V.A.M.), St George\u2019s Hospital Medical School, London, UK; Yannis Protonotarios Medical Center, Hora Naxos, Naxos, Greece (N.P., A.T.); and Genetics Team, Section of Epidemiology, Institute of Cancer Research, Royal Marsden Hospital, Sutton, Surrey, UK (R.S.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"McKenna","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiological Sciences (A.S.C., E.W.A.N., R.K.M., W.J.M.), Dermatology (S.C.), Pathology (M.I.O.), and Medical Genetics (V.A.M.), St George\u2019s Hospital Medical School, London, UK; Yannis Protonotarios Medical Center, Hora Naxos, Naxos, Greece (N.P., A.T.); and Genetics Team, Section of Epidemiology, Institute of Cancer Research, Royal Marsden Hospital, Sutton, Surrey, UK (R.S.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","unstructured":"Fontaine G Guiraudon G Frank R Vedel J Grosgogeat Y Cabrol C Facquet J. 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