J Clin Endocrinol Metab. 2014 Aug 5:jc20142094. [Epub ahead of print]
Frequency of AIP gene mutations in young patients with acromegaly: a registry-based study.
Schöfl C1, Honegger J, Droste M, Grussendorf M, Finke R, Plöckinger U, Berg C, Willenberg HS, Lammert A, Klingmüller D, Jaursch-Hancke C, Tönjes A,Schneidewind S, Flitsch J, Bullmann C, Dimopoulou C, Stalla G, Mayr B, Hoeppner W, Schopohl J.
Context: Familial and sporadic growth hormone-secreting pituitary adenomas are associated with mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene. Patients with an AIP mutation (AIPmut) tend to have more aggressive tumours occurring at younger age. Objective: To investigate the frequency of AIPmut in patients diagnosed at ≤ 30 years of age. Design: The German Acromegaly Registry database (1795 patients in 58 centers) was screened for patients diagnosed with acromegaly at ≤ 30 years of age (329 patients). Sixteen centers participated and 91 patients consented to AIPmut analysis. Intervention: DNA was analysed by direct sequencing and multiplex ligation dependent probe amplification Main outcome Measures: Number of patients with AIPmut Results: Five patients had either a mutation (c.490C>T, c.844C>T, and c.911G>A, 3 males) or gross deletions of exon 1 and 2 of the AIP gene (n=2, 1 female). The overall frequency of an AIPmut was 5.5 %, and in patients with an apparently sporadic adenoma or macroadenoma 2.3 % or 2.4 %, respectively. By contrast, 3 of 4 patients (75 %) with a positive family history were tested positive for an AIPmut. Except for a positive family history there were no significant differences between patients with and without an AIPmut. Conclusions: The frequency of AIPmut in this registry-based cohort of young patients with acromegaly is lower than previously reported. Patients with a positive family history should be tested for an AIPmut, while young patients without an apparent family history should be screened depending on the individual cost-benefit ratio.
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