{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T21:03:21Z","timestamp":1761512601521,"version":"build-2065373602"},"reference-count":21,"publisher":"BMJ","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1998,11]]},"abstract":"<jats:p>Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by tumours of the parathyroid glands, the anterior pituitary, and endocrine pancreas. The MEN1 gene has recently been cloned and germline mutations have been identified in MEN1 patients in the United States, Canada, and Europe. We examined MEN1 gene mutations in MEN1 and MEN1 related cases in eight unrelated Japanese families. These families include five familial MEN1 (FMEN1), two sporadic MEN1 (SMEN1), and one familial hyperparathyroidism (FHP). Direct sequence analysis of the protein coding regions was carried out in all the probands. We identified six different heterozygous mutations in the coding region, of which five were novel, including one missense mutation (E45G) in both FMEN1 and SMEN1, three deletions (569del, 711del, and 1350del3) in FMEN1 and FHP, and two nonsense mutations (R29X and Y312X) in FMEN1 and SMEN1. Only one of these mutations (Y312X) has previously been reported. One proband with FMEN1 had no mutation in the entire exon sequence including the 5' and 3' untranslated regions. A restriction digestion analysis of 19 relatives from the five families showed a close correlation between the existence of the MEN1 gene mutation and disease onset. Four different polymorphisms, including two novel ones, were identified. These findings imply that a diversity of MEN1 gene mutations exists in Japanese MEN1 and MEN1 related disease, suggesting that analysis of the entire coding region of the MEN1 gene is required for genetic counselling in Japan.<\/jats:p>","DOI":"10.1136\/jmg.35.11.915","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:37:21Z","timestamp":1226331441000},"page":"915-919","source":"Crossref","is-referenced-by-count":25,"title":["Identification of five novel germline mutations of the MEN1 gene in Japanese multiple endocrine neoplasia type 1 (MEN1) families."],"prefix":"10.1136","volume":"35","author":[{"given":"M","family":"Sato","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Matsubara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Miyauchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Ohye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Imachi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Murao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Takahara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1998,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/0002-9343(54)90353-8","article-title":"Genetic aspects of adenomatosis of endocrine glands","volume":"16","author":"Wermer, P.","year":"1954","unstructured":"Wermer P. Genetic aspects of adenomatosis of endocrine glands. Am J Med 1954;16:363-7.","journal-title":"Am J Med"},{"key":"ref_2","first-page":"481","article-title":"Familial multiple endocrine adenoma peptic ulcer complex","volume":"43","author":"Ballard, H.S.; Frame, B.; Hartsock, R.J.","year":"1964","unstructured":"Ballard HS, Frame B, Hartsock RJ. Familial multiple endocrine adenoma peptic ulcer complex. Am J Med 1964;43: 481-516.","journal-title":"Am J Med"},{"key":"ref_3","first-page":"591","article-title":"Multiple endocrine neoplasia type 1: clinical features and management","author":"Metz, D.C.; Jensen, R.T.; Bale, A.","year":"1994","unstructured":"Metz DC, Jensen RT, Bale A, et al. Multiple endocrine neoplasia type 1: clinical features and management. In: Bilezekain JP, Levine MA, Marcus R, eds. The parathyroids. New York: Raven Press, 1994:591-646."},{"key":"ref_4","first-page":"85","article-title":"Multiple endocrine neoplasia type I maps to chromosome 11 and is lost in insulinoma","volume":"332","author":"Larsson, C.; Skogscid, B.; Oberg, K.","year":"1988","unstructured":"Larsson C, Skogscid B, Oberg K, et al. Multiple endocrine neoplasia type I maps to chromosome 11 and is lost in insulinoma. Nature 1988;332:85-7. Identification offive novel germline mutations of the MENI gene","journal-title":"Nature; Identification offive novel germline mutations of the MENI gene"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1126\/science.276.5311.404","article-title":"Positional cloning of the gene for multiple endocrine neoplasia type 1","volume":"276","author":"Chandrasekharrapa, S.C.; Guru, S.C.; Manickam, P.","year":"1997","unstructured":"Chandrasekharrapa SC, Guru SC, Manickam P, et al. Positional cloning of the gene for multiple endocrine neoplasia type 1. Science 1997;276:404-7.","journal-title":"Science"},{"key":"ref_6","first-page":"1437","article-title":"Hereditary cancer, oncogenes, and antioncogenes","volume":"45","author":"Knudson, A.G.","year":"1985","unstructured":"Knudson AG. Hereditary cancer, oncogenes, and antioncogenes. Cancer Res 1985;45:1437-43.","journal-title":"Cancer Res"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1056\/NEJM198907273210402","article-title":"Clonality of parathyroid tumors in familial multiple endocrine neoplasia type 1","volume":"321","author":"Friedman, E.; Sakaguchi, K.; Bale, A.E.","year":"1989","unstructured":"Friedman E, Sakaguchi K, Bale AE, et al. Clonality of parathyroid tumors in familial multiple endocrine neoplasia type 1. N EnglJ Med 1989;321:213-18.","journal-title":"N EnglJ Med"},{"key":"ref_8","first-page":"6804","article-title":"Allelic loss from chromosome 11 in parathyroid tumors","volume":"52","author":"Friedman, E.; De-Marco, L.; Gejman, P.V.","year":"1992","unstructured":"Friedman E, De-Marco L, Gejman PV, et al. Allelic loss from chromosome 11 in parathyroid tumors. Cancer Res 1992;52:6804-9.","journal-title":"Cancer Res"},{"key":"ref_9","first-page":"1968","article-title":"Localization of the MEN 1 gene to a small region within chromosome 1 1q13 by deletion","volume-title":"mapping in tumors. Proc Natl Acad Sci","volume":"87","author":"Bystrom, C.; Larsson, C.; Blomberg, C.","year":"1990","unstructured":"Bystrom C, Larsson C, Blomberg C, et al. Localization of the MEN 1 gene to a small region within chromosome 1 1q13 by deletion mapping in tumors. Proc Natl Acad Sci USA 1990;87: 1968-72."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1093\/hmg\/6.7.1169","article-title":"Germline mutations of the MENI gene in familial multiple endocrine neoplasia type 1 and related states","volume":"6","author":"Agarwal, S.K.; Kester, M.B.; Debelenko, L.V.","year":"1997","unstructured":"Agarwal SK, Kester MB, Debelenko LV, et al. Germline mutations of the MENI gene in familial multiple endocrine neoplasia type 1 and related states. Hum Mol Genet 1997;6:1169-75.","journal-title":"Hum Mol Genet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1093\/hmg\/6.7.1177","article-title":"Identification of the multiple endocrine neoplasia type 1 (MEN1) gene","volume":"6","author":"Lemmens, I.; Van de Ven, W.J.M.; Kas, K.","year":"1997","unstructured":"Lemmens I, Van de Ven WJM, Kas K, et al. Identification of the multiple endocrine neoplasia type 1 (MEN1) gene. Hum Mol Genet 1997;6:1177-83.","journal-title":"Hum Mol Genet"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/363458a0","article-title":"Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A","volume":"363","author":"Mulligan, L.M.; Kwok, J.B.; Healey, C.S.","year":"1993","unstructured":"Mulligan LM, Kwok JB, Healey CS, et al. Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature 1993;363:458-60.","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S0196-9781(97)00263-5","article-title":"et aL Molecular cloning and gene expression of growth hormone-releasing peptide receptor in rat tissues","volume":"19","author":"Yokote, R.; Sato, M.; Matsubara, S.","year":"1998","unstructured":"Yokote R, Sato M, Matsubara S, et aL Molecular cloning and gene expression of growth hormone-releasing peptide receptor in rat tissues. Peptides 1998;19:15-20.","journal-title":"Peptides"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8093","DOI":"10.1093\/nar\/17.20.8093","article-title":"Detection of minority point mutations by modified PCR technique: a new approach for a sensitive diagnosis of tumorprogression markers","volume":"17","author":"Haliassos, A.; Chomel, J.C.; Grandjouan, S.","year":"1989","unstructured":"Haliassos A, Chomel JC, Grandjouan S, et al. Detection of minority point mutations by modified PCR technique: a new approach for a sensitive diagnosis of tumorprogression markers. Nucleic Acids Res 1989;17:8093-9.","journal-title":"Nucleic Acids Res"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1111\/j.1469-1809.1994.tb00730.x","article-title":"Age of onset in familial adenomatous polyposis: heterogeneity within families and among APC mutations","volume":"58","author":"Presciuttini, S.; Varesco, L.; Sala, P.","year":"1994","unstructured":"Presciuttini S, Varesco L, Sala P, et al. Age of onset in familial adenomatous polyposis: heterogeneity within families and among APC mutations. Ann Hum Genet 1994;58:331-42.","journal-title":"Ann Hum Genet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1038\/bjc.1996.173","article-title":"Familial testicular cancer in Norway and southern Sweden","volume":"73","author":"Heimdal, K.; Olsson, H.; Tretli, S.","year":"1996","unstructured":"Heimdal K, Olsson H, Tretli S, et al. Familial testicular cancer in Norway and southern Sweden. BrJ Cancer 1996;73: 964-9.","journal-title":"BrJ Cancer"},{"key":"ref_17","first-page":"990","article-title":"Anticipation in familial leukemia","volume":"59","author":"Horwitz, M.; Goode, E.L.; Jarvik, G.P.","year":"1996","unstructured":"Horwitz M, Goode EL, Jarvik GP. Anticipation in familial leukemia. AmJHum Genet 1996;59:990-8.","journal-title":"AmJHum Genet"},{"key":"ref_18","first-page":"3487","article-title":"A large multiple endocrine neoplasia type 1 family with clinical expression suggestive of anticipation","volume":"82","author":"Giraud, S.; Choplin, H.; Teh, B.T.","year":"1997","unstructured":"Giraud S, Choplin H, Teh BT, et al. A large multiple endocrine neoplasia type 1 family with clinical expression suggestive of anticipation. Clin Endocrinol Metab 1997;82: 3487-92.","journal-title":"Clin Endocrinol Metab"},{"key":"ref_19","first-page":"653","article-title":"Clinical studies of multiple endocrine neoplasia type","volume":"89","author":"Trump, D.; Farren, B.; Wooding, C.","year":"1996","unstructured":"Trump D, Farren B, Wooding C, et al. Clinical studies of multiple endocrine neoplasia type 1 (MENl). Q J7 Med 1996;89:653-9."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1056\/NEJM198208123070707","article-title":"Familial hypocalciuric hypercalcemia: the relation to primary parathyroid hyperplasia","volume":"307","author":"Marx, S.J.; Attie, M.F.; Spiegel, A.M.","year":"1982","unstructured":"Marx SJ, Attie MF, Spiegel AM, et al. Familial hypocalciuric hypercalcemia: the relation to primary parathyroid hyperplasia. N EnglJ Med 1982;307:416-26.","journal-title":"N EnglJ Med"},{"key":"ref_21","first-page":"468","article-title":"A kindred with a variant of multiple endocrine neoplasia type 1 demonstrating frequent expression of pituitary tumors but not linked to the multiple endocrine neoplasia type 1 locus on chromosome region 1 1q13. Jf Clin Endocrinol Metab","volume":"82","author":"Stock, J.L.; Warth, M.R.; Teh, B.T.","year":"1997","unstructured":"Stock JL, Warth MR, Teh BT, et al. A kindred with a variant of multiple endocrine neoplasia type 1 demonstrating frequent expression of pituitary tumors but not linked to the multiple endocrine neoplasia type 1 locus on chromosome region 1 1q13. Jf Clin Endocrinol Metab 1997;82:468-92."}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.35.11.915","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T04:19:24Z","timestamp":1759724364000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.35.11.915"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,11]]},"references-count":21,"journal-issue":{"issue":"11","published-online":{"date-parts":[[1998,11,1]]},"published-print":{"date-parts":[[1998,11]]}},"alternative-id":["10.1136\/jmg.35.11.915"],"URL":"https:\/\/doi.org\/10.1136\/jmg.35.11.915","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"type":"print","value":"0022-2593"},{"type":"electronic","value":"1468-6244"}],"subject":[],"published":{"date-parts":[[1998,11]]}}}