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Genetic analyses in patients with familial isolated hyperparathyroidism and hyperparathyroidism–jaw tumour syndrome
Author(s) -
Mizusawa Noriko,
Uchino Shinya,
Iwata Takeo,
Tsuyuguchi Masaru,
Suzuki Yasuyo,
Mizukoshi Tsunenori,
Yamashita Yoshio,
Sakurai Akihiro,
Suzuki Shinichi,
Beniko Mutsuo,
Tahara Hideki,
Fujisawa Masato,
Kamata Nobuyuki,
Fujisawa Kenji,
Yashiro Tohru,
Nagao Daisuke,
Golam Hossain Md.,
Sano Toshiaki,
Noguchi Shiro,
Yoshimoto Katsuhiko
Publication year - 2006
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2006.02534.x
Subject(s) - germline mutation , frameshift mutation , germline , men1 , missense mutation , primary hyperparathyroidism , hyperparathyroidism , medicine , mutation , endocrinology , parathyroid adenoma , parathyroid carcinoma , adenoma , multiple endocrine neoplasia , genetics , biology , gene
Summary Background A subset of familial isolated primary hyperparathyroidism (FIHP) is a variant of hyperparathyroidism–jaw tumour syndrome (HPT‐JT). Aim/patients and methods We investigated the involvement of the HRPT2 , MEN1 and CASR genes in 11 provisional FIHP families and two HPT‐JT families. Results Germline mutations of HRPT2 were found in two of the 11 FIHP families and one of the two HPT‐JT families. One FIHP family with parathyroid carcinoma and atypical adenomas and another FIHP family with cystic parathyroid adenoma had novel frameshift mutations of 518–521del and 62–66del, respectively. In a patient with HPT‐JT, a de novo germline mutation of 39delC was detected. Novel somatic HRPT2 mutations of 70–73del and 95–102del were found in two of five parathyroid tumours in a family with a 518–521del mutation. Biallelic inactivation of HRPT2 by a combination of germline and somatic mutation was confirmed in the parathyroid tumours. The finding that two families diagnosed with FIHP carried HRPT2 mutations suggests that they have occult HPT‐JT. In the remaining 10 families, one family had a missense MEN1 mutation. No mutations of CASR were detected. Conclusion Our results confirm the need to test for HRPT2 in FIHP families, especially those with parathyroid carcinomas, atypical adenomas or adenomas with cystic change.