Urbani C, Russo D, Raggi F, Lombardi M, Sardella C, Scattina I, Lupi I, Manetti L, Tomisti L, Marcocci C, Martino E, Bogazzi F
Section of Endocrinology, Department of Clinical and Experimental Medicine, University of Pisa, Ospedale Cisanello, Via Paradisa 2, 56124, Pisa, Italy,
J Endocrinol Invest. 2014 Oct;37(10):949-55. doi: 10.1007/s40618-014-0123-4. Epub 2014 Jul 5.
Acromegaly usually occurs as a sporadic disease, but it may be a part of familial pituitary tumor syndromes in rare cases. Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene have been associated with a predisposition to familial isolated pituitary adenoma. The aim of the present study was to evaluate the AIP gene in a patient with gigantism and in her relatives.
Direct sequencing of AIP gene was performed in fourteen members of the family, spanning among three generations.
The index case was an 18-year-old woman with gigantism due to an invasive GH-secreting pituitary adenoma and a concomitant tall-cell variant of papillary thyroid carcinoma. A novel germline mutation in the AIP gene (c.685C>T, p.Q229X) was identified in the proband and in two members of her family, who did not present clinical features of acromegaly or other pituitary disorders. Eleven subjects had no mutation in the AIP gene. Two members of the family with clinical features of acromegaly refused either the genetic or the biochemical evaluation. The Q229X mutation was predicted to generate a truncated AIP protein, lacking the last two tetratricopeptide repeat domains and the final C-terminal α-7 helix.
We identified a new AIP germline mutation predicted to produce a truncated AIP protein, lacking its biological properties due to the disruption of the C-terminus binding sites for both the chaperones and the client proteins of AIP.
肢端肥大症通常为散发性疾病，但在极少数情况下可能是家族性垂体瘤综合征的一部分。芳烃受体相互作用蛋白（AIP）基因的种系突变与家族性孤立性垂体腺瘤的易感性有关。本研究的目的是评估一名巨人症患者及其亲属的AIP基因。
对该家族三代人中的14名成员进行AIP基因直接测序。
索引病例是一名18岁女性，因侵袭性生长激素分泌型垂体腺瘤及伴发的甲状腺乳头状癌高细胞变体而患巨人症。在先证者及其两名家族成员中鉴定出AIP基因的一种新的种系突变（c.685C>T，p.Q229X），这两名家族成员没有肢端肥大症或其他垂体疾病的临床特征。11名受试者的AIP基因无突变。两名有肢端肥大症临床特征的家族成员拒绝进行基因或生化评估。预测Q229X突变会产生截短的AIP蛋白，缺少最后两个四肽重复结构域和最后的C末端α-7螺旋。
我们鉴定出一种新的AIP种系突变，预测该突变会产生截短的AIP蛋白，由于AIP伴侣蛋白和客户蛋白的C末端结合位点被破坏，该蛋白缺乏其生物学特性。
