Endocrine Abstracts

Introduction: Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a rare autosomal-dominant disorder caused by mutations in CDC73 tumor suppressor gene. To date about 80 mutations in CDC73 have been described.

Case reports: Four patients among a cohort of young patients (<40 y.o.) with primary hyperparathyroidism (PHPT) underwent next-generation sequencing (NGS) (Ion Torrent^TM PGM^TM, Thermo Fisher Scientific–Life Technologies, USA) using a custom-designed Ion AmpliSeq^TM gene panel.

Case 1. A female with PHPT manifestation at age 20, osteitis fibrosa cystica (OFC), kidney microlithiasis, serum Ca 4.09 mmol/l (2.15–2.55), parathyroid hormone (PTH) 2440 pg/ml (15–65) due to parathyroid carcinoma, and endometrial polyp at diagnosis. At age 26 her PHPT recurred as lung metastases of parathyroid carcinoma, requiring surgical intervention. Case 2. A female with PHPT manifestation at age 24, severe OFC, kidney microlithiasis, serum Ca 3.36 mmol/l, Ca²⁺1.56 mmol/l (1.03–1.29), PTH 558.8 pg/ml due to parathyroid carcinoma. A patient had positive family history, with polycystic kidney disease in her mother. Case 3. A male with PHPT manifestation at age 22, severe OFC, serum Ca 3.9 mmol/l, Ca²⁺1.84 mmol/l, PTH 1441 pg/ml due to parathyroid carcinoma. Case 4. A female with mild PHPT manifestation at age 30, serum Ca 2.94 mmol/l, Ca²⁺1.24 mmol/l, PTH 125.1 pg/ml due to single parathyroid hyperplasia.

NGS revealed four heterozygous germline CDC73 mutations, respectively: a novel nonsense mutation in exon 3 p.R91X, a nonsense mutation in exon 6 p.Q166X, a novel nonsense mutation in exon 7 p.R229X and a novel missense mutation in exon 8 p.R263C.

Conclusion: We describe four cases of HPT-JT in young patients with PHPT in Russia. 3 of 4 mutations are described for the first time. Occurrence of nonsense CDC73 mutations in patients with parathyroid carcinoma and a missense mutation in a patient with parathyroid hyperplasia may reflect various degrees of parafibromin dysfunction.