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 89 publications

(98 citation statements)

References 38 publications

(121 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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

View full text Add to dashboard Cite

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.

show abstract

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

View full text Add to dashboard Cite

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

“…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

View full text Add to dashboard Cite

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

Cited by 89 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

Contact Info

Product

Resources

About