Hyperparathyroidism–jaw tumor syndrome: a report of three large kindred

Iacobone, Maurizio; Masi, Giulia; Barzon, Luisa; Porzionato, Andrea; Macchi, Veronica; Ciarleglio, Francesco Antonio; Palù, Giorgio; De, Raffaele; Viel, Giovanni; Favia, Gennaro

doi:10.1007/s00423-009-0511-y

Cited by 91 publications

(100 citation statements)

References 38 publications

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“…In one study, a mean age at diagnosis of 36 years is reported (17). The median age at diagnosis of HPT was 28.5 years (range in our study; this is in accordance with recently published data (17).…”

Section: Clinical Findingssupporting

confidence: 93%

CDC73-related hereditary hyperparathyroidism: five new mutations and the clinical spectrum

Frank‐Raue¹,

Haag²,

Schulze³

et al. 2011

European Journal of Endocrinology

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Objective: Hyperparathyroidism-jaw tumour (HPT-JT) syndrome is a rare autosomal dominant cause of benign and malignant parathyroid tumours, ossifying jaw tumours, various cystic and neoplastic renal abnormalities and benign and malignant uterine tumours. Disease-causing mutations have been localised in the tumour suppressor gene CDC73. There is limited information available on the mutations, and resulting phenotypes and long-term follow-up data are especially scarce. Design: We analysed the clinical data from 16 patients (including three families) carrying mutations in the CDC73 gene. We describe five new mutations/gene variants, the corresponding phenotypes of these carriers and the long-term follow-up. Methods: The 16 patients were evaluated at an endocrine outpatient clinic and at a surgical department. DNA samples were obtained for sequence analysis of the CDC73 gene. Results: Clinical features of HPT-JT syndrome were detected in 13 of the 15 carriers with germline CDC73 mutations. The major features were benign (nZ7; 47%) or cancerous (nZ3; 20%) HPT-JT was present in eight cases (53%). Most patients had severe hypercalcaemia, and median serum calcium levels were 3.36 mmol/l. A patient with non-secretory parathyroid carcinoma was included. HPT was diagnosed at a median age of 28.5 years. Mutational analysis of the CDC73 gene identified eight sequence changes, three of them have been reported previously, whereas five are novel: c.1346delG, c.88_94delTTCTCCT, the non-coding variants, c.307C5GOT and c.424K5TOC and c.*12COA of unknown significance. Conclusions: This study significantly increases the information available on the mutations and phenotypes of HPT-JT syndrome.

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Section: Clinical Findingssupporting

confidence: 93%

CDC73-related hereditary hyperparathyroidism: five new mutations and the clinical spectrum

Frank‐Raue¹,

Haag²,

Schulze³

et al. 2011

European Journal of Endocrinology

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“…Patients with HPT-JT syndrome have a 15-24% chance of developing parathyroid carcinoma, and loss of heterozygosity of chromosome 1q, the location of the HRPT2/CDC73 gene, is reported to be found in 55% of parathyroid carcinomas. 1,17,[19][20][21] The calcium-sensing receptor (CASR) regulates not only the synthesis and secretion of parathyroid hormone, but also the proliferation of the parathyroid glands. We have previously reported that 31% of parathyroid carcinomas had irregular or absent staining for CASR compared with only 1% of sporadic adenomas.…”

mentioning

confidence: 99%

Downregulation of CASR expression and global loss of parafibromin staining are strong negative determinants of prognosis in parathyroid carcinoma

et al. 2011

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Parathyroid carcinoma is associated with mutations in the HRPT2/CDC73 gene and with decreased parafibromin and calcium-sensing receptor (CASR) expression, but in some cases establishing an unequivocal diagnosis remains a challenge. The aim of our study was to evaluate the prognostic value of CASR and parafibromin expression and of HRPT2/CDC73 mutations in patients with an established diagnosis of parathyroid carcinoma. Data on survival and disease-free survival were obtained from hospital records of 23 patients with an established diagnosis of parathyroid carcinoma in whom CASR and parafibromin expression and HRPT2/CDC73 mutation analyses were available from paraffin-embedded pathological specimens. KaplanMeier curves were used for survival analysis. Downregulation of CASR expression, global loss of parafibromin staining and a HRPT2/CDC73 mutation were, respectively, found in 7 (30%), 13 (59%) and 4 (17%) patients, and were associated with, respectively, 16-fold, 4-fold and 7-fold increased risk of developing local or distant metastasis. These findings suggest that although downregulation of CASR expression, global loss of parafibromin staining and mutations in the HRPT2/CDC73 gene are tools of proven value to assist in establishing a diagnosis of parathyroid carcinoma, their absence does not exclude it. Notwithstanding, we demonstrate a significant added value of these markers as strong determinants of increased malignant potential and thus as negative prognostic markers in this malignancy.

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“…In a Dutch kindred with HPT-JT, Hürtle cell thyroid adenoma was identified [22]. In a large Italian unrelated HPT-JT kindred, thyroid adenoma and PTC were also found [23]. However, association of PTC with HPT-JT has not been determined so far.…”

Section: Discussionmentioning

confidence: 96%

Early-onset, severe, and recurrent primary hyperparathyroidism associated with a novel <i>CDC73</i> mutation

et al. 2015

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Hyperparathyroidism–jaw tumor syndrome: a report of three large kindred

Cited by 91 publications

References 38 publications

CDC73-related hereditary hyperparathyroidism: five new mutations and the clinical spectrum

CDC73-related hereditary hyperparathyroidism: five new mutations and the clinical spectrum

Downregulation of CASR expression and global loss of parafibromin staining are strong negative determinants of prognosis in parathyroid carcinoma

Early-onset, severe, and recurrent primary hyperparathyroidism associated with a novel <i>CDC73</i> mutation

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