Title :

A large extended family with hyperparathyroidism-jaw tumor syndrome due to deletion of the third exon of cdc73: clinical and molecular features

Author(s) :

Le Collen, Lauriane [Auteur]
Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID) - UMR 8199
Barraud, Sara [Auteur]
Centre de Recherche en Sciences et Technologies de l'Information et de la Communication - EA 3804 [CRESTIC]
Braconnier, Antoine [Auteur]
Hôpital universitaire Robert Debré [Reims] [CHU Reims]
Coppin, Lucie [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277
Zachar, Dominique [Auteur]
Université de Reims Champagne-Ardenne [URCA]
Boulagnon, Camille [Auteur]
Université de Reims Champagne-Ardenne [URCA]
Deguelte, Sophie [Auteur]
Université de Reims Champagne-Ardenne [URCA]
Souchon, Pierre Francois [Auteur]
Spodenkiewicz, Marta [Auteur]
Poirsier, Celine [Auteur]
Hôpital universitaire Robert Debré [Reims] [CHU Reims]
Aubert, Sebastien [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277
Odou, Marie-Francoise [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Delemer, Brigitte [Auteur]
Centre de Recherche en Sciences et Technologies de l'Information et de la Communication - EA 3804 [CRESTIC]

Journal title :

Endocrine

Abbreviated title :

Endocrine

Volume number :

73

Pages :

693–701

Publication date :

2021-05-17

ISSN :

1559-0100

Keyword(s) :

Knudson two-hit hypothesis
Large rearrangements
CDC73
Hyperparathyroidism
Jaw Tumors
HRPT2

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

OBJECTIVE: We described the phenotype of a large 4-generation family with Hyperparathyrodism-Jaw Tumor syndrome (HPT-JT) associated with a rare deletion of exon 3 of the CDC73 gene. METHODS: We collected medical, genetic ...
Show more >OBJECTIVE: We described the phenotype of a large 4-generation family with Hyperparathyrodism-Jaw Tumor syndrome (HPT-JT) associated with a rare deletion of exon 3 of the CDC73 gene. METHODS: We collected medical, genetic data on 24 family members descended from a common ancestor carrying a heterozygous deletion of exon 3. RESULTS: Thirteen carried the deletion, the penetrance was estimated at 50% at 40 years. Seven patients (39 ± 14.5 years) presented with HPT which could start at 13. Median plasmatic calcium and PTH levels were 3.13 ± 0.7 mmol/L and 115 ± 406 pg/ml, respectively. Kidney disease related to hypercalcemia were present in 57.1% of patients. All seven patients underwent surgery to remove a single parathyroid adenoma. One recurrence occurred 7 years post-surgery. No parathyroid carcinoma has been found to date. We found two atypical parathyroid adenomas. We described an additional somatic variant in exon 1 of gene CDC73 in two tumors. Jaw tumors were not necessarily associated with hyperparathyroidism, as shown in one case. Two kidney cysts were also reported. Variable phenotype expressivity was emphasized by clinical presentations in 2 monozygotic twins: acute hypercalcemia, kidney failure and ossifying fibroma in one twin, versus normocalcemic parathyroid adenoma in the other one. CONCLUSIONS: We report a family carrier of a deletion of exon 3 of the CDC73 gene. This is characterized by a high level of hypercalcemia, deleterious kidney effects and atypical parathyroid adenomas without carcinomas. Onset and intensity of HPT remain unpredictable. The additional somatic mutation found in the parathyroid tumor could lead to these phenotypical variations.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CNRS
Université de Lille

Collections :

• Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277
• Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID) - UMR 8199
• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Submission date :

2021-07-06T12:50:53Z
2024-01-24T10:13:19Z