Department of Endocrinology, Centre Hospitalier Universitaire de Liège, Domaine Universitaire du Sart-Tilman, University of Liège, 4000 Liège, Belgium.
Eur J Endocrinol. 2011 Oct;165(4):509-15. doi: 10.1530/EJE-11-0304. Epub 2011 Jul 13.
Aryl hydrocarbon receptor interacting protein (AIP) mutations (AIPmut) cause aggressive pituitary adenomas in young patients, usually in the setting of familial isolated pituitary adenomas. The prevalence of AIPmut among sporadic pituitary adenoma patients appears to be low; studies have not addressed prevalence in the most clinically relevant population. Hence, we undertook an international, multicenter, prospective genetic, and clinical analysis at 21 tertiary referral endocrine departments.
We included 163 sporadic pituitary macroadenoma patients irrespective of clinical phenotype diagnosed at <30 years of age.
Overall, 19/163 (11.7%) patients had germline AIPmut; a further nine patients had sequence changes of uncertain significance or polymorphisms. AIPmut were identified in 8/39 (20.5%) pediatric patients. Ten AIPmut were identified in 11/83 (13.3%) sporadic somatotropinoma patients, in 7/61 (11.5%) prolactinoma patients, and in 1/16 non-functioning pituitary adenoma patients. Large genetic deletions were not seen using multiplex ligation-dependent probe amplification. Familial screening was possible in the relatives of seven patients with AIPmut and carriers were found in six of the seven families. In total, pituitary adenomas were diagnosed in 2/21 AIPmut-screened carriers; both had asymptomatic microadenomas.
Germline AIPmut occur in 11.7% of patients <30 years with sporadic pituitary macroadenomas and in 20.5% of pediatric patients. AIPmut mutation testing in this population should be considered in order to optimize clinical genetic investigation and management.
芳香烃受体相互作用蛋白 (AIP) 突变 (AIPmut) 可导致年轻患者的侵袭性垂体腺瘤，通常发生在家族性孤立性垂体腺瘤的背景下。AIPmut 在散发性垂体腺瘤患者中的患病率似乎较低；研究尚未解决最具临床相关性人群中的患病率问题。因此，我们在 21 个三级内分泌科进行了国际、多中心、前瞻性遗传和临床分析。
我们纳入了 163 名年龄<30 岁诊断为散发性垂体大腺瘤的患者，无论其临床表现如何。
总体而言，163 名患者中有 19 名（11.7%）存在种系 AIPmut；另有 9 名患者存在意义不明的序列改变或多态性。在 39 名儿科患者中发现了 8 个 AIPmut。在 11/83（13.3%）的散发性生长激素腺瘤患者、7/61（11.5%）的催乳素瘤患者和 1/16 名无功能垂体腺瘤患者中发现了 10 个 AIPmut。未使用多重连接依赖性探针扩增检测到大片段基因缺失。在 7 名携带 AIPmut 患者的亲属中进行了家族筛查，并在其中 6 个家庭中发现了携带者。在携带 AIPmut 的 21 名患者中，共诊断出 2 例垂体腺瘤；两者均为无症状微腺瘤。
30 岁以下的散发性垂体大腺瘤患者中，种系 AIPmut 的发生率为 11.7%，儿科患者中的发生率为 20.5%。在该人群中应考虑进行 AIPmut 突变检测，以便优化临床遗传调查和管理。
