A large extended family with hyperparathyroidism-jaw tumor syndrome due to deletion of the third exon of CDC73: clinical and molecular features.
CDC73
HRPT2
Hyperparathyroidism
Jaw Tumors
Knudson two-hit hypothesis.
Large rearrangements
Journal
Endocrine
ISSN: 1559-0100
Titre abrégé: Endocrine
Pays: United States
ID NLM: 9434444
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
12
04
2021
accepted:
05
05
2021
pubmed:
18
5
2021
medline:
21
9
2021
entrez:
17
5
2021
Statut:
ppublish
Résumé
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. We collected medical, genetic data on 24 family members descended from a common ancestor carrying a heterozygous deletion of exon 3. 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. 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.
Identifiants
pubmed: 33999366
doi: 10.1007/s12020-021-02756-4
pii: 10.1007/s12020-021-02756-4
doi:
Substances chimiques
CDC73 protein, human
0
Tumor Suppressor Proteins
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
693-701Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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