Department of Endocrinology Diabetology, University of Reims, Reims, France.
Inserm/CNRS UMR 1283/8199, Institut Pasteur de Lille, EGID, Lille, France.
Endocrine. 2021 Sep;73(3):693-701. doi: 10.1007/s12020-021-02756-4. Epub 2021 May 17.
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.
我们描述了一个大型 4 代家族的表型，该家族患有伴 CDC73 基因外显子 3 缺失的甲状旁腺功能亢进-颌骨肿瘤综合征（HPT-JT）。
我们收集了 24 名来自携带外显子 3 杂合缺失的共同祖先的家族成员的医学和遗传数据。
13 人携带缺失，40 岁时的外显率估计为 50%。7 名患者（39±14.5 岁）出现 HPT，可在 13 岁时发病。中位血浆钙和 PTH 水平分别为 3.13±0.7mmol/L 和 115±406pg/ml。57.1%的患者存在与高钙血症相关的肾脏疾病。所有 7 名患者均接受手术切除单个甲状旁腺瘤。术后 7 年发生 1 例复发。迄今为止尚未发现甲状旁腺癌。我们发现了 2 例非典型甲状旁腺瘤。我们在 2 个肿瘤中描述了基因 CDC73 外显子 1 的额外体细胞变异。正如 1 例所示，颌骨肿瘤不一定与甲状旁腺功能亢进相关。还报告了 2 例肾囊肿。2 对同卵双胞胎的临床表现强调了可变的表型表达：1 对双胞胎表现为急性高钙血症、肾衰竭和骨化纤维瘤，而另 1 对双胞胎则表现为正常血钙甲状旁腺瘤腺瘤。
我们报告了一个携带 CDC73 基因外显子 3 缺失的家族。其特征是高钙血症水平、有害的肾脏影响和非典型甲状旁腺瘤而无癌。HPT 的发病和强度仍不可预测。在甲状旁腺瘤中发现的额外体细胞突变可能导致这些表型变异。
