Sarquis Marta S, Silveira Leticia G, Pimenta Flavio J, Dias Eduardo P, Teh Bin T, Friedman Eitan, Gomez Ricardo S, Tavares Gabriela C, Eng Charis, De Marco Luiz
Department of Medicine, Surgery, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Surgery. 2008 May;143(5):630-40. doi: 10.1016/j.surg.2007.12.012. Epub 2008 Mar 17.
Familial forms of hyperparathyroidism are responsible for approximately 10% of the cases of primary hyperparathyroidism, and their management is different from the sporadic forms. Our objective was to study the gene sequence and expression of HRPT2 and clinical outcome regarding recurrence or persistence rates in three Brazilian kindreds with familial hyperparathyroidism after up to 30 years of follow-up.
Clinical and biochemical data, direct sequencing of germline DNA of the HRPT2 gene, and analysis of parafibromin expression (HRPT2 gene product) using RT-PCR and immunohistochemistry of resected parathyroid neoplasms were performed.
Affected members of kindred A were found to carry a novel, germline, nonsense mutation in exon 1 (c.96G>A; W32X) of HRPT2. Six of seven patients who have undergone less than total parathyroidectomy recurred after up to 30 years of follow-up. An unrelated affected patient from kindred B had a germline mutation in exon 7 (c.686delGAGT), and the disease recurred with several pulmonary metastases after 5 years follow-up. The affected member of kindred C also had a previously described mutation in exon 7 (c.679delAG) and the disease recurred after 10 years of follow-up. All parathyroid neoplasms from these families had diffuse loss of expression by immunohistochemistry.
An unacceptable recurrence/persistence rate (80%) associated with increasingly difficult re-operations and risk of parathyroid carcinoma in the setting of germline mutations of HRPT2 gene with familial hyperparathyroidism suggest that a more aggressive operative approach should be undertaken in these patients. Parafibromin immunohistochemistry may serve as a cost-effective screen for HRPT2-related aggressive parathyroid disease.
家族性甲状旁腺功能亢进约占原发性甲状旁腺功能亢进病例的10%，其治疗方法与散发性病例不同。我们的目的是研究HRPT2的基因序列和表达，以及在三个巴西家族性甲状旁腺功能亢进家族中随访长达30年后的复发或持续率的临床结果。
进行了临床和生化数据、HRPT2基因种系DNA的直接测序，以及使用逆转录聚合酶链反应（RT-PCR）分析甲状旁腺素表达（HRPT2基因产物）和对切除的甲状旁腺肿瘤进行免疫组织化学分析。
发现家系A的患病成员在HRPT2基因第1外显子中携带一种新的种系无义突变（c.96G>A；W32X）。在接受次全甲状旁腺切除术的7名患者中，有6名在长达30年的随访后复发。家系B的一名无关患病患者在第7外显子中有一个种系突变（c.686delGAGT），疾病在随访5年后复发并伴有多处肺转移。家系C的患病成员在第7外显子中也有一个先前描述的突变（c.679delAG），疾病在随访10年后复发。这些家族的所有甲状旁腺肿瘤经免疫组织化学分析均显示表达弥漫性缺失。
在家族性甲状旁腺功能亢进患者中，HRPT2基因种系突变导致不可接受的复发/持续率（80%），再次手术难度越来越大且有甲状旁腺癌风险，这表明对这些患者应采取更积极的手术方法。甲状旁腺素免疫组织化学可作为一种经济有效的筛查HRPT2相关侵袭性甲状旁腺疾病的方法。
