{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T21:17:04Z","timestamp":1778275024814,"version":"3.51.4"},"reference-count":30,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2003,10]]},"abstract":"<jats:p>Mendelian forms of hypertension have delivered a treasure trove of novel genes. To date, the molecular mechanisms of five such syndromes have been largely clarified, including glucocorticoid-remediable aldosteronism, Liddle's syndrome, apparent mineralocorticoid excess, an activating mutation of the mineralocorticoid receptor, and pseudohypoaldosteronism type 2. Each of these conditions features salt sensitivity with increased sodium and volume reabsorption by the kidney and low plasma renin activity. None of the gene loci for these syndromes has been convincingly linked to hypertension in the general population. We are investigating kindreds who have autosomal-dominant hypertension and brachydactyly. Affected persons invariably have both anomalies. The hypertension is severe and results in death at about age 50 years from stroke. The condition resembles essential hypertension, because renin, aldosterone, and norepinephrine responses are normal and no salt sensitivity is present. The response to antihypertensive drugs is general. Another feature is diminished baroreflex sensitivity with markedly impaired blood pressure buffering. Furthermore, the ventrolateral medulla may be compromised in these patients, because neurovascular anomalies are a regular finding. We mapped the gene(s) for this disease to chromosome 12p and narrowed the chromosomal region by studying more affected families. Interestingly, the same locus was recently mapped in Chinese families with essential hypertension. Our 3-centimorgan region contains genes encoding a phosphodiesterase, an ATP-dependent potassium channel, and its regulator the sulfonylurea receptor 2. Screening of the coding regions revealed that none of these candidate genes harbor obvious mutations; however, other genetic mechanisms may nevertheless compromise their function. Our study underscores the importance of regulatory physiology to the understanding of a complex genetic syndrome.<\/jats:p>","DOI":"10.1152\/ajpregu.00174.2003","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T20:31:29Z","timestamp":1425414689000},"page":"R709-R714","source":"Crossref","is-referenced-by-count":10,"title":["Mendelian hypertension with brachydactyly as a molecular genetic lesson in regulatory physiology"],"prefix":"10.1152","volume":"285","author":[{"given":"Friedrich C.","family":"Luft","sequence":"first","affiliation":[{"name":"The Clinical Research Center of the Franz Volhard Clinic and Max Delbr\u00fcck Center for Molecular Medicine, HELIOS Klinikum, Medical Faculty of the Charit\u00e9, Humboldt University of Berlin, 13125 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Okan","family":"Toka","sequence":"additional","affiliation":[{"name":"The Clinical Research Center of the Franz Volhard Clinic and Max Delbr\u00fcck Center for Molecular Medicine, HELIOS Klinikum, Medical Faculty of the Charit\u00e9, Humboldt University of Berlin, 13125 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hakan R.","family":"Toka","sequence":"additional","affiliation":[{"name":"The Clinical Research Center of the Franz Volhard Clinic and Max Delbr\u00fcck Center for Molecular Medicine, HELIOS Klinikum, Medical Faculty of the Charit\u00e9, Humboldt University of Berlin, 13125 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"Jordan","sequence":"additional","affiliation":[{"name":"The Clinical Research Center of the Franz Volhard Clinic and Max Delbr\u00fcck Center for Molecular Medicine, HELIOS Klinikum, Medical Faculty of the Charit\u00e9, Humboldt University of Berlin, 13125 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvia","family":"B\u00e4hring","sequence":"additional","affiliation":[{"name":"The Clinical Research Center of the Franz Volhard Clinic and Max Delbr\u00fcck Center for Molecular Medicine, HELIOS Klinikum, Medical Faculty of the Charit\u00e9, Humboldt University of Berlin, 13125 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"REF1","unstructured":"Bahring S, Nagai T, Toka HR, Nitz I, Toka O, Aydin A, Muhl A, Wienker TF, Schuster H, and Luft FC.Deletion at 12p in a Japanese child with brachydactyly overlaps the assigned locus of brachydactyly with hypertension in a Turkish family.Am J Hum Genet60: 732-751, 1997."},{"key":"REF2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199604253341701"},{"key":"REF3","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.10.3.253"},{"key":"REF4","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19971219)73:3<279::AID-AJMG10>3.0.CO;2-G"},{"key":"REF5","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0173(86)90005-6"},{"key":"REF6","unstructured":"Cushing H.Concerning a definite regulatory mechanism of the vasomotor center, which controls blood pressure during cerebral compression.Johns Hopkins Hosp Bull12: 290-292, 1901."},{"key":"REF7","doi-asserted-by":"publisher","DOI":"10.1016\/0753-3322(96)82592-3"},{"key":"REF8","unstructured":"Dittmar C.Ueber die Lage des sogenannten Gef\u00e4sscentrums in der Medulla oblongata: Berichte ueber die Verhandlungen der koeniglich saechischen Gesellschaft der Wissenschaften zu Leipzig.Math Phys Klasse25: 449-469, 1873."},{"key":"REF9","doi-asserted-by":"publisher","DOI":"10.1227\/00006123-198006000-00001"},{"key":"REF10","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)11343-5"},{"key":"REF11","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg135"},{"key":"REF12","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1977.03270400035014"},{"key":"REF13","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.82.12.1363"},{"key":"REF14","doi-asserted-by":"publisher","DOI":"10.1097\/00000658-198503000-00023"},{"key":"REF15","unstructured":"Jannetta PJ, Segal R, Wolfson SK, Dujovny M, and Semba A.Neurogenic hypertension: etiology and surgical treatment II. Observations in an experimental nonhuman primate model.Ann Surg201: 254-261, 1985."},{"key":"REF16","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-200204000-00028"},{"key":"REF17","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000012126.56352.FD"},{"key":"REF18","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.102.21.2611"},{"key":"REF19","unstructured":"Julius Sand Johnson EH.Stress, autonomic hyperactivity and essential hypertension: an enigma.J Hypertens3,Suppl4: 11-17, 1985."},{"key":"REF20","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.19.5718"},{"key":"REF21","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00241-0"},{"key":"REF22","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320550106"},{"key":"REF23","doi-asserted-by":"crossref","unstructured":"Nagy Z, Busjahn A, Bahring S, Faulhaber HD, Gohlke HR, Knoblauch H, Rosenthal M, Muller-Myhsok B, Schuster H, and Luft FC.Quantitative trait loci for blood pressure exist near the IGF-1, the Liddle syndrome, the angiotensin II-receptor gene and the renin loci in man.J Am Soc Nephrol10: 1709-1716, 1999.","DOI":"10.1681\/ASN.V1081709"},{"key":"REF24","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.28.9.1749"},{"key":"REF25","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1998.00732.x"},{"key":"REF26","doi-asserted-by":"publisher","DOI":"10.1038\/ng0596-98"},{"key":"REF27","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.28.6.1085"},{"key":"atypb1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa021559"},{"key":"atypb2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jhh.1001271"},{"key":"REF30","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-129-3-199808010-00008"}],"container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpregu.00174.2003","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,1]],"date-time":"2022-05-01T09:31:51Z","timestamp":1651397511000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpregu.00174.2003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,10]]},"references-count":30,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2003,10]]}},"alternative-id":["10.1152\/ajpregu.00174.2003"],"URL":"https:\/\/doi.org\/10.1152\/ajpregu.00174.2003","relation":{},"ISSN":["0363-6119","1522-1490"],"issn-type":[{"value":"0363-6119","type":"print"},{"value":"1522-1490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,10]]}}}