Browsing by Subject "somatotropinooma"

Recently, our group reported that mutations in KCNQ1, a potassium channel gene usually linked to long QT syndrome, cause growth hormone deficiency and maternally inherited gingival fibromatosis. Expression of the mutated KCNQ1 with KCNE2 subunit was shown to reduce pituitary hormone secretion in functional experiments in the original study. The aim of this thesis was to investigate if germline mutations in KCNQ1 and KCNE2, a gene encoding an auxiliary potassium channel subunit, could also play a role in the opposite phenomenon, growth hormone excess. Growth hormone (GH) excess causes acromegaly, a condition that is typically due to a GH secreting pituitary adenoma. I screened KCNQ1 and KCNE2 for germline mutations in 45 acromegaly patients by Sanger sequencing and predicted effects of the mutations on protein function by in silico tools. Only deep intronic and synonymous polymorphisms were detected in KCNQ1. These findings were likely insignificant based on the in silico predictions and the variants’ frequencies in the general population. In KCNE2, a heterozygous c.22A>G, p.(Thr8Ala) mutation with an unknown significance was found in two patients. It was present in the general population with a frequency of 0.0038. In conclusion, no evidence of KCNQ1 or KCNE2 mutations being associated with growth hormone excess was found. Mutation screenings of larger patient series and additional functional experiments are needed to shed more light on the roles of KCNQ1 related genes in growth hormone secretion.