{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:12:49Z","timestamp":1783555969905,"version":"3.55.0"},"reference-count":18,"publisher":"BMJ","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1998,4]]},"abstract":"<jats:p>Testotoxicosis is a form of male precocious puberty caused by heterogeneous activating mutations in the gene for the lutrophin\/choriogonadotrophin receptor (LHR). A patient with an unusually early and severe presentation of testotoxicosis, including profound Leydig cell hyperplasia, was found to have a sporadic mutation encoding Asp578--&gt;Tyr. The severe testotoxicosis phenotype appears to be related to the strongly activating nature of the Tyr substitution.<\/jats:p>","DOI":"10.1136\/jmg.35.4.340","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:37:21Z","timestamp":1226331441000},"page":"340-341","source":"Crossref","is-referenced-by-count":43,"title":["Severe testotoxicosis phenotype associated with Asp578--&gt;Tyr mutation of the lutrophin\/choriogonadotrophin receptor gene."],"prefix":"10.1136","volume":"35","author":[{"given":"J","family":"M\u00fcller","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Gondos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Kosugi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Mori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Shenker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[1998,4,1]]},"reference":[{"key":"ref_1","first-page":"191","article-title":"Gonadotropin-independent precocious puberty. Endocrinol Metab Clin North","volume":"20","author":"Fl, Holland","year":"1991","unstructured":"Holland Fl. Gonadotropin-independent precocious puberty. Endocrinol Metab Clin North Am 1991;20:191-210.","journal-title":"Am"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1038\/365652a0","article-title":"A constitutively activating mutation of the luteinizing hormone receptor in familial male precocious puberty","volume":"365","author":"Shenker, A.; Laue, L.; Kosugi, S.; JJ, Jr, Merendino; Minegishi, T.; GB, Jr, Cutler","year":"1993","unstructured":"Shenker A, Laue L, Kosugi S, Merendino JJ Jr, Minegishi T, Cutler GB Jr. A constitutively activating mutation of the luteinizing hormone receptor in familial male precocious puberty. Nature 1993;365:652-4.","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1093\/hmg\/2.11.1779","article-title":"Cosegregation of missense mutations of the luteinizing hormone receptor gene with familial male-limited precocious puberty","volume":"2","author":"Kremer, H.; Mariman, E.; Otten, B.J.","year":"1993","unstructured":"Kremer H, Mariman E, Otten BJ, et al. Cosegregation of missense mutations of the luteinizing hormone receptor gene with familial male-limited precocious puberty. Hum Mol Genet 1993;2:1779-83.","journal-title":"Hum Mol Genet"},{"key":"ref_4","first-page":"1906","article-title":"Genetic heterogeneity of constitutively activating mutations of the human luteinizing hormone receptor in familial","volume-title":"male-limited precocious puberty. Proc Nal Acad Sci","volume":"92","author":"Laue, L.; Chan, W.Y.; Hsueh, A.J.W.","year":"1995","unstructured":"Laue L, Chan WY, Hsueh AJW, et al. Genetic heterogeneity of constitutively activating mutations of the human luteinizing hormone receptor in familial male-limited precocious puberty. Proc Nal Acad Sci USA 1995;92:1906-10."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1136\/jmg.33.2.143","article-title":"A new point mutation in the luteinising hormone receptor gene in familial and sporadic male limited precocious puberty: genotype does not always correlate with phenotype","volume":"33","author":"Evans, B.A.J.; Bowen, D.J.; Smith, P.J.; Clayton, P.E.; Gregory, J.","year":"1996","unstructured":"Evans BAJ, Bowen DJ, Smith PJ, Clayton PE, Gregory J. A new point mutation in the luteinising hormone receptor gene in familial and sporadic male limited precocious puberty: genotype does not always correlate with phenotype. JMed Genet 1996;33:143-7.","journal-title":"JMed Genet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1530\/eje.0.1340533","article-title":"Luteinizing hormone receptor mutations and sex differentiation","volume":"134","author":"Themmen, A.P.N.; Brunner, H.G.","year":"1996","unstructured":"Themmen APN, Brunner HG. Luteinizing hormone receptor mutations and sex differentiation. Eur Jf Endocrinol 1996;134:533-40.","journal-title":"Eur Jf Endocrinol"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1111\/j.1651-2227.1994.tb13192.x","article-title":"Hazards of ketoconozole therapy in testotoxicosis","volume":"83","author":"Babovic-Vuksanovic, D.; Donaldson, M.D.; Gibson, N.A.; Wallace, A.M.","year":"1994","unstructured":"Babovic-Vuksanovic D, Donaldson MD, Gibson NA, Wallace AM. Hazards of ketoconozole therapy in testotoxicosis. Acta Paediatr Scand 1994;83:994-7.","journal-title":"Acta Paediatr Scand"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1177\/000992289503400509","article-title":"Testotoxicosis: an unusual presentation and novel gene mutation","volume":"34","author":"Clark, P.A.; Clarke, W.L.","year":"1995","unstructured":"Clark PA, Clarke WL. Testotoxicosis: an unusual presentation and novel gene mutation. Clin Pediatr 1995;34:271-4.","journal-title":"Clin Pediatr"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1210\/jcem-52-2-271","article-title":"Testicular Leydig cell hyperplasia as a cause of familial sexual precocity","volume":"52","author":"Schedewie, H.K.; Reiter, E.O.; Beitins, I.Z.","year":"1981","unstructured":"Schedewie HK, Reiter EO, Beitins IZ, et al. Testicular Leydig cell hyperplasia as a cause of familial sexual precocity. Jf Clin Endocrinol Metab 1981;52:271-8.","journal-title":"Jf Clin Endocrinol Metab"},{"key":"ref_10","first-page":"9905","article-title":"Testicular changes in gonadotropin-independent familial male sexual precocity","volume":"109","author":"Gondos, B.; Egli, C.A.; Rosenthal, S.M.; Grumbach, M.M.","year":"1985","unstructured":"Gondos B, Egli CA, Rosenthal SM, Grumbach MM. Testicular changes in gonadotropin-independent familial male sexual precocity. Arch Pathol Lab Med 1985;109:9905.","journal-title":"Arch Pathol Lab Med"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"31813","DOI":"10.1074\/jbc.271.50.31813","article-title":"The role of Asp57' in maintaining the inactive conformation of the human lutropin\/choriogonadotropin receptor","volume":"271","author":"Kosugi, S.; Mori, T.; Shenker, A.","year":"1996","unstructured":"Kosugi S, Mori T, Shenker A. The role of Asp57' in maintaining the inactive conformation of the human lutropin\/choriogonadotropin receptor. Jf Biol Chem 1996; 271:31813-17.","journal-title":"Jf Biol Chem"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1093\/protein\/10.5.501","article-title":"A model of the lutropin\/choriogonadotropin receptor: insights into the structural and functional effects of constitutively activating mutations","volume":"10","author":"Lin, Z.; Shenker, A.; Pearlstein, R.","year":"1997","unstructured":"Lin Z, Shenker A, Pearlstein R. A model of the lutropin\/choriogonadotropin receptor: insights into the structural and functional effects of constitutively activating mutations. Protein Eng 1997;10:501-10.","journal-title":"Protein Eng"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/S0950-351X(95)80519-2","article-title":"G protein-coupled receptor structure and function: the impact of disease-causing mutations","volume":"9","author":"Shenker, A.","year":"1995","unstructured":"Shenker A. G protein-coupled receptor structure and function: the impact of disease-causing mutations. Baillieres Clin Endocrinol Metab 1995;9:427-51.","journal-title":"Baillieres Clin Endocrinol Metab"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/S0002-9394(14)73708-0","article-title":"Ocular findings in patients with autosomal dominant retinitis pigmentosa and rhodopsin, proline-347leucine","volume":"111","author":"Berson, E.L.; Rosner, B.; Sandberg, M.A.; Weigel-DiFranco, C.; Dryja, T.P.","year":"1991","unstructured":"Berson EL, Rosner B, Sandberg MA, Weigel-DiFranco C, Dryja TP. Ocular findings in patients with autosomal dominant retinitis pigmentosa and rhodopsin, proline-347leucine. Am J Ophthalmol 1991;111:614-23.","journal-title":"Am J Ophthalmol"},{"key":"ref_15","first-page":"1934","article-title":"Clinical expression correlates with location of rhodopsin mutation in dominant retinitis pigmentosa","volume":"36","author":"Sandberg, M.A.; Weigel-DiFranco, C.; Dryja, T.P.; Berson, E.L.","year":"1995","unstructured":"Sandberg MA, Weigel-DiFranco C, Dryja TP, Berson EL. Clinical expression correlates with location of rhodopsin mutation in dominant retinitis pigmentosa. Invest Ophthalmol Vis Sci 1995;36:1934-42.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/367639a0","article-title":"Rhodopsin mutation G9OD and a molecular mechanism for congenital night blindness","volume":"367","author":"Rao, V.R.; Cohen, G.B.; Oprian, D.D.","year":"1994","unstructured":"Rao VR, Cohen GB, Oprian DD. Rhodopsin mutation G9OD and a molecular mechanism for congenital night blindness. Nature 1994;367:639-42.","journal-title":"Nature"},{"key":"ref_17","first-page":"2577","article-title":"Somatic and germline mutations of the TSH receptor gene in thyroid diseases","volume":"80","author":"J, Van Sande; J, Parma; M, Tonacchera; S, Swillens; J, Dumont; G, Vassart","year":"1995","unstructured":"Van Sande J, Parma J, Tonacchera M, Swillens S, Dumont J, Vassart G. Somatic and germline mutations of the TSH receptor gene in thyroid diseases. 7 Clin Endocrinol Metab 1995;80:2577-85.","journal-title":"7 Clin Endocrinol Metab"},{"key":"ref_18","first-page":"54754","article-title":"Functional characteristics of three new germline mutations of the thyrotropin receptor gene causing autosomal dominant toxic thyroid hyperplasia","volume":"81","author":"Tonacchera, M.; Van Sande, J.; Cetani, F.","year":"1996","unstructured":"Tonacchera M, Van Sande J, Cetani F, et al. Functional characteristics of three new germline mutations of the thyrotropin receptor gene causing autosomal dominant toxic thyroid hyperplasia. 7 Clin Endocrinol Metab 1996;81:54754.","journal-title":"7 Clin Endocrinol Metab"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.35.4.340","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T17:33:47Z","timestamp":1760722427000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.35.4.340"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,4]]},"references-count":18,"journal-issue":{"issue":"4","published-online":{"date-parts":[[1998,4,1]]},"published-print":{"date-parts":[[1998,4]]}},"alternative-id":["10.1136\/jmg.35.4.340"],"URL":"https:\/\/doi.org\/10.1136\/jmg.35.4.340","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,4]]}}}