Lauriane Le Collen1,2, Sara Barraud3,4, Antoine Braconnier5, Lucie Coppin6, Dominique Zachar7, Camille Boulagnon7, Sophie Deguelte8, Pierre François Souchon9, Marta Spodenkiewicz10, Céline Poirsier10, Sébastien Aubert11, Marie Françoise Odou12, Brigitte Delemer13,14. 1. Department of Endocrinology Diabetology, University of Reims, Reims, France. lle-collen@chu-reims.fr. 2. Inserm/CNRS UMR 1283/8199, Institut Pasteur de Lille, EGID, Lille, France. lle-collen@chu-reims.fr. 3. Department of Endocrinology Diabetology, University of Reims, Reims, France. 4. CRESTIC EA 3804, University of Reims Champagne Ardenne, UFR Sciences Exactes et Naturelles, Moulin de La Housse, BP 1039, 51687, Reims Cedex 2, France. 5. Department of Nephrology, University of Reims, Reims, France. 6. Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277 - CANTHER - Cancer - Heterogeneity Plasticity and Resistance to Therapies, F-59000, Lille, France. 7. Laboratory of Pathology, University of Reims, Reims, France. 8. Department of Surgery, University of Reims, Reims, France. 9. Department of Pediatrics, University of Reims, Reims, France. 10. Department of Genetics, University of Reims, Reims, France. 11. Laboratory of Pathology, University of Lille, Lille, France. 12. Univ. Lille, Inserm, CHU Lille, U1286 - Infinite - Institute for Translational Research in Inflammation, F-59000, Lille, France. 13. Department of Endocrinology Diabetology, University of Reims, Reims, France. bdelemer@chu-reims.fr. 14. CRESTIC EA 3804, University of Reims Champagne Ardenne, UFR Sciences Exactes et Naturelles, Moulin de La Housse, BP 1039, 51687, Reims Cedex 2, France. bdelemer@chu-reims.fr.
Abstract
PURPOSE: 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. CONCLUSION: 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.
PURPOSE: 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. CONCLUSION: 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.
Authors: C J Haven; F K Wong; E W van Dam; R van der Juijt; C van Asperen; J Jansen; C Rosenberg; M de Wit; J Roijers; J Hoppener; C J Lips; C Larsson; B T Teh; H Morreau Journal: J Clin Endocrinol Metab Date: 2000-04 Impact factor: 5.958
Authors: J Szabó; B Heath; V M Hill; C E Jackson; R J Zarbo; L E Mallette; S L Chew; G M Besser; R V Thakker; V Huff Journal: Am J Hum Genet Date: 1995-04 Impact factor: 11.025