Genetic analyses in patients with familial isolated hyperparathyroidism and hyperparathyroidism-jaw tumor syndrome
Germline mutation of HRPT2 in patients with hyperparathyroidism
Germline mutation of HRPT2 in patients with HPT
Uchino, Shinya Noguchi Thyroid Clinic and Hospital Foundation
Tsuyuguchi, Masaru Tokushima Municipal Hospital
Suzuki, Yasuyo Sapporo Medical University
Mizukoshi, Tsunenori Sapporo Medical University
Yamashita, Yoshio Saga University
Sakurai, Akihiro Shinshu University
Suzuki, Shinichi Fukushima Medical University
Beniko, Mutsuo Kin-ikyo Sapporo Hospital
Tahara, Hideki Osaka City University
Fujisawa, Masato Kawasaki Medical School
鎌田, 伸之 Hiroshima University
Yashiro, Tohru University of Tsukuba
長尾, 大輔 The University of Tokushima
Golam, Hossain Md. The University of Tokushima
Noguchi, Shiro Noguchi Thyroid Clinic and Hospital Foundation
A subset of familial isolated primary hyperparathyroidism (FIHP) is a variant of hyperparathyroidism-jaw tumor syndrome (HPT-JT).
Aim/Patients and Methods
We investigated the involvement of the HRPT2, MEN1, and CASR genes in provisional 11 FIHP families and 2 HPT-JT families.
Germline mutations of HRPT2 were found in 2 of 11 FIHP families and 1 of 2 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 2 of 5 parathyroid tumors in a family with 518-521del mutation. Biallelic inactivation of HRPT2 by a combination of germline mutation and somatic mutation was confirmed in parathyroid tumors. The finding that 2 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.
Our results confirm the need to test for HRPT2 in FIHP families, especially in those with parathyroid carcinomas, atypical adenomas, or adenomas with cystic change.
John Wiley & Sons
This is the peer reviewed version of the following article: Mizusawa N, Uchino S, Iwata T, Tsuyuguchi M, Suzuki Y, Mizukoshi T, Yamashita Y, Sakurai A, Suzuki S, Beniko M, Tahara H, Fujisawa M, Kamata N, Fujisawa K, Yashiro T, Nagao D, Golam HM, Sano T, Noguchi S, Yoshimoto K. Clin Endocrinol. 2006;65:9-16., which has been published in final form at https://doi.org/10.1111/j.1365-2265.2006.02534.x. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
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