Introduction: Hyperparathyroidism-jaw tumour syndrome (HPT-JT) is a rare disorder, which is frequently characterized by the development of parathyroid carcinomas and atypical parathyroid adenomas and, thus, severe course of primary hyperparathyroidism (PHPT).
Case reports: Two patients (1 male and 1 female, 18 y.o. and 13 y.o. at the time of diagnosis of PHPT, respectively) among a cohort of young patients (<40 y.o.) with PHPT, underwent next-generation sequencing (NGS) (Ion TorrentTM PGMTM, Thermo Fisher ScientificLife Technologies, USA) using a custom-designed Ion AmpliSeqTM gene panel. NGS did not reveal any pathogenic variants in genes associated with familial PHPT in these two patients, but the analysis of the sequence data by the ExomeDepth program [Plagnol V et al, 2012] allowed us to assume the existence of large deletions in CDC73 gene. To confirm this observation MLPA (MRC-Holland, the Netherlands) of CDC73 on ABI 3500xL Genetic Analyzer (Applied Biosystems, USA) was performed. In a male with severe PHPT (serum total calcium 4.49 mmol/l (2.152.55), ionized calcium 2.03 mmol/l (1.031.29), PTH 1833 pg/ml (1565), osteitis fibrosa cystica) and histological diagnosis of atypical parathyroid adenoma, a gross deletion including the entire CDC73 gene and four additional genes (TROVE2, GLRX2, B3GALT2 and LINK0103) was detected. In a female with severe PHPT (serum total calcium 3.57 mmol/l, ionized calcium 1.58 mmol/l, PTH 1550 pg/ml, osteitis fibrosa cystica) and histological diagnosis of parathyroid carcinoma, the deletion of 110 exons of CDC73 gene was detected. The patients mother also had PHPT due to parathyroid adenoma.
Conclusion: These two cases illustrate that NGS data could be successfully applied for indirect assessment of large gene deletions which could be further confirmed by MLPA. Search for CDC73 mutations is necessary among patients with parathyroid carcinomas and atypical parathyroid adenomas, which could occur at any age.
20 - 23 May 2017
European Society of Endocrinology