{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T22:08:32Z","timestamp":1761862112967},"reference-count":18,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2001,12,24]],"date-time":"2001-12-24T00:00:00Z","timestamp":1009152000000},"content-version":"vor","delay-in-days":1057,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[1999,2]]},"abstract":"<jats:sec><jats:title>BACKGROUND AND OBJECTIVES<\/jats:title><jats:p>Familial hyperparathyroidism may occur as familial isolated hyperparathyroidism (FIHP) or as part of an inherited syndrome, in particular multiple endocrine neoplasia types 1 and 2\u2003A (MEN1, MEN2A) and hyperparathyroidism\u2013jaw tumour (HPT\u2013JT) syndrome. The localization of the genes responsible for these syndromes has enabled genetic screening of families with primary hyperparathyroidism (PHPT) to be carried out. This has important clinical implications in terms of individual follow\u2010up and management. We previously reported a large FIHP family with an increased risk of parathyroid cancer and excluded its linkage to MEN1, MEN2 and PTH genes. Here we re\u2010analysed this family and performed genetic linkage to the HPT\u2013JT locus in chromosome 1q21\u2010q32. Loss of heterozygosity studies of 1q21\u2010q32, 11q13 and X chromosome were also performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>PATIENTS AND DESIGN<\/jats:title><jats:p>We studied 19 family members, aged 6\u201363 years. High molecular weight DNA was isolated from peripheral blood samples from 17 family members. For the two deceased individuals, DNA was extracted from normal paraffin embedded tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>MEASUREMENTS<\/jats:title><jats:p>All individuals (except two deceased patients) had serum corrected calcium, inorganic phosphate, intact PTH, prolactin and various pancreatic hormones, measured on fasting blood samples. Twenty microsatellite markers were examined for the 1q21\u2010q32 region, the locus for the HPT\u2013JT gene. Genetic polymorphisms were determined by polymerase chain reaction amplification of genomic DNA and genetic linkage analysis was performed. Loss of heterozygosity studies were performed using paraffin\u2010embedded parathyroid tissues from four affected members.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Seven of the eight affected family members included in this study had biochemical evidence of PHPT and surgically proven parathyroid tumours. Indication of linkage of the disease to the HPT\u2013JT locus was demonstrated with a maximum lod score of 2.32 by two\u2010points linkage analysis. Linkage data were supported by multi\u2010point analysis which gave a maximum lod score of 2.7. Meiotic recombinations detected in one affected individual narrowed the region to 26\u2003cM. As a result of the genetic findings, we re\u2010screened the living family members by orthopantomograph and renal ultrasound, and identified two jaw lesions in two gene carriers. One affected family member demonstrated polycystic kidney disease, thus establishing the association between the two conditions. A reduced penetrance of HPT in females was evident, in agreement with our previous study. No allelic deletion was detected in any tumour at 1q21\u2010q32, 11q13 or X chromosome.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>This study illustrates the usefulness and importance of genetic studies in familial isolated hyperparathyroidism families. Our clinical and genetic findings indicate that this previously reported familial isolated hyperparathyroidism family has hyperparathyroidism\u2013jaw tumour syndrome.<\/jats:p><\/jats:sec>","DOI":"10.1046\/j.1365-2265.1999.00633.x","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T09:46:50Z","timestamp":1027676810000},"page":"191-196","source":"Crossref","is-referenced-by-count":48,"title":["Genetic studies of a family with hereditary hyperparathyroidism\u2013jaw tumour syndrome"],"prefix":"10.1111","volume":"50","author":[{"given":"Wassif S.","family":"Wassif","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filip","family":"Farnebo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Tean Teh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caje F.","family":"Moniz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang\u2010Yuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John D.","family":"Harrison","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy J.","family":"Peters","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catharina","family":"Larsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip","family":"Harris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2001,12,24]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117890"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5311.404"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1159\/000185462"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004390050369"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0694supp-246"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002689900188"},{"key":"e_1_2_6_8_2","first-page":"1006","article-title":"Hereditary hyperparathyroidism and multiple ossifying jaw fibromas: a clinically and genetically distinct syndrome","volume":"108","author":"Jackson C.E.","year":"1990","journal-title":"Surgery"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.33.123"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.1994.tb02570.x"},{"key":"e_1_2_6_11_2","first-page":"1347","article-title":"Parametric and non parametric linkage analysis: a unified multi\u2010point approach","volume":"58","author":"Kruglyak L.","year":"1996","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_6_12_2","first-page":"703","article-title":"Multiple endocrine neoplasia","volume":"9","author":"Larsson C.","year":"1990","journal-title":"Cancer Surveys"},{"key":"e_1_2_6_13_2","unstructured":"Mallette L.E.(1994) The functional and pathologic spectrum of parathyroid abnormalities in hyperparathyroidism. In:The Parathyroids: Basic and Clinical Concepts(eds J.P.Bilezikian R.Marcus & M.A.Levine). New York: Raven pp.423455."},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.3.5766.87"},{"key":"e_1_2_6_15_2","first-page":"A75","article-title":"Follow\u2010up of two hyperparathyroidism\u2013jaw tumour syndrome families reported in 1971 and 1981 reveals that they are related and that parathyroid cancer is a part of the syndrome","volume":"57","author":"Pidwirny G.N.","year":"1995","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0046-8177(94)90219-4"},{"key":"e_1_2_6_17_2","first-page":"944","article-title":"Hereditary hyperparathyroidism\u2010jaw\u2013tumour syndrome: the endocrine\u2010tumour gene HRPT2 maps to chromosome 1q21\u2010q31","volume":"56","author":"Szabo J.","year":"1995","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.81.12.4204"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.77.6.1485"}],"container-title":["Clinical Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1046%2Fj.1365-2265.1999.00633.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1046%2Fj.1365-2265.1999.00633.x","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1046\/j.1365-2265.1999.00633.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,28]],"date-time":"2023-10-28T22:02:26Z","timestamp":1698530546000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1046\/j.1365-2265.1999.00633.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,2]]},"references-count":18,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1999,2]]}},"alternative-id":["10.1046\/j.1365-2265.1999.00633.x"],"URL":"https:\/\/doi.org\/10.1046\/j.1365-2265.1999.00633.x","archive":["Portico"],"relation":{},"ISSN":["0300-0664","1365-2265"],"issn-type":[{"value":"0300-0664","type":"print"},{"value":"1365-2265","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,2]]}}}