Aryl hydrocarbon receptor interacting protein (AIP) gene mutation analysis in children and adolescents with sporadic pituitary adenomas
Aryl hydrocarbon receptor interacting protein (AIP) gene mutation analysis in children and adolescents with sporadic pituitary adenomas
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DOI：
10.1111/j.1365-2265.2008.03266.x
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发表时间：
2008-10-01
影响因子：
3.2
通讯作者：
Aaltonen, Lauri A.
中科院分区：
文献类型：
--
作者：
Georgitsi, Marianthi;De Menis, Ernesto;Aaltonen, Lauri A.
目的垂体腺瘤少见于儿童和青少年。最近发现，垂体腺瘤易感性（PAP）与芳香烃受体相互作用蛋白（AIP）基因的生殖细胞突变有关。本研究的目的是检查生殖系AIP突变的比例明显散发的儿科垂体adenoma.Design基因组DNA中的AIP基因突变进行了分析，通过PCR扩增和直接测序patients-a人口为基础的队列组成的36个明显散发的儿科垂体腺瘤患者，提到两个医疗中心在意大利，被列入本研究。患者要么小于18年的诊断，或显示临床证据的腺瘤发展之前的年龄为18 years.Results杂合框内缺失Y248 del（c.742_744delTAC）被确定在GH分泌腺瘤患者。肿瘤DNA的杂合性丢失（洛）分析显示野生型等位基因的丢失。携带突变的一级亲属在临床上induced.Conclusions虽然突变不存在于非生长激素分泌腺瘤患者，生殖系AIP突变可以发现在儿童和青少年生长激素分泌肿瘤，即使在没有家族史。本研究报告了单一种族患者的AIP突变分析结果。显然，需要进一步的研究来提高我们对AIP在儿童垂体腺瘤中作用的认识。
Objective Pituitary adenomas occur rarely in childhood and adolescence. Pituitary adenoma predisposition (PAP) has been recently associated with germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene. The aim of the study was to examine the proportion of germline AIP mutations in apparently sporadic paediatric pituitary adenomas.Design Genomic DNA was analysed for mutations in the AIP gene, by PCR amplification and direct sequencing.Patients A population-based cohort consisting of 36 apparently sporadic paediatric pituitary adenoma patients, referred to two medical centres in Italy, was included in the study. Patients were either less than 18 years at diagnosis, or showed clinical evidence of adenoma development before the age of 18 years.Results A heterozygous in-frame deletion Y248del (c.742_744delTAC) was identified in one GH-secreting adenoma patient. Loss of heterozygosity (LOH) analysis of tumour DNA revealed the loss of the wild-type allele. First degree relatives carrying the mutation were clinically unaffected.Conclusions While mutations were absent in non-GH-secreting adenoma patients, germline AIP mutations can be found in children and adolescents with GH-secreting tumours, even in the absence of family history. The present study reports the AIP mutation analysis results on patients of a single ethnic origin. Clearly, further studies are needed to improve our knowledge on the role of AIP in paediatric pituitary adenomas.