Prevalence of AIP mutations in a series of Turkish acromegalic patients: are synonymous AIP mutations relevant?

Abstract

In sporadic acromegaly, overall AIP(mut) prevalence is reported as 3, 4.1 and 16% in studies carried out across Europe. However, it is not known whether the prevalence shows any changes across different ethnicities. The aim of the study was to identify prevalence of AIP(mut) in a series of Turkish acromegalic patients. Direct sequencing of AIP gene was performed in 92 sporadic acromegalic patients. One patient was found to have a new mutation in exon 6: g67.258,286 (G/A) heterozygote; (GGC/GAC; gly/asp). Apart from this new mutation, previously defined synonymous mutations in AIP gene were detected in seven patients (Exon 4; rs2276020; (GAC/GAT; asp/asp) and six patients were found to have five different intronic mutations in AIP gene which were not previously defined. The patient with pathogenic AIP(mut) presented at a young age and had an aggressive and treatment resistant tumour. The prevalence of AIP(mut) in Turkish patients was found to be 1% in sporadic acromegaly in the present study. In addition, one synonymous mutation which was previously defined and six new intronic mutations have been described in Turkish acromegalic patients. All acromegalic patients with synonymous AIP(mut) presented with macroadenoma and majority of them had invasive tumour. The prevalence of AIP(mut) in Turkish patients was found to be 1% in sporadic acromegaly in the present study. This ratio increases when younger age groups are taken into account 6% among patients <30years of age at the time of diagnosis of acromegaly. The clinical features of acromegaly, such as having large and invasive tumours, may be affected by the presence of synonymous AIP(mut).