Screening for germline KCNQ1 and KCNE2 mutations in a set of somatotropinoma patients
Objective: Recently, mutations in KCNQ1, a potassium channel gene usually linked to long QT syndrome, were reported to cause maternally inherited gingival fibromatosis and growth hormone deficiency (GHD). Expression of the mutated KCNQ1 with the auxiliary potassium channel subunit KCNE2 was shown to...
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doaj-aa93e0b0dcf3468692f67109c86580d32020-11-24T23:08:03ZengBioscientificaEndocrine Connections2049-36142049-36142018-04-017564565210.1530/EC-18-0123Screening for germline KCNQ1 and KCNE2 mutations in a set of somatotropinoma patientsAnna-Pauliina Iivonen0Johanna Känsäkoski1Atte Karppinen2Leena Kivipelto3Camilla Schalin-Jäntti4Auli Karhu5Taneli Raivio6Institute of Biomedicine/Physiology, Biomedicum Helsinki, University of Helsinki, Helsinki, FinlandInstitute of Biomedicine/Physiology, Biomedicum Helsinki, University of Helsinki, Helsinki, FinlandDepartment of Neurosurgery, Helsinki University Hospital, Helsinki, FinlandDepartment of Neurosurgery, Helsinki University Hospital, Helsinki, FinlandDepartment of Endocrinology, Abdominal Center, University of Helsinki and Helsinki University Hospital, Helsinki, FinlandDepartment of Medical and Clinical Genetics, RPU, Biomedicum Helsinki, University of Helsinki, Helsinki, FinlandInstitute of Biomedicine/Physiology, Biomedicum Helsinki, University of Helsinki, Helsinki, FinlandObjective: Recently, mutations in KCNQ1, a potassium channel gene usually linked to long QT syndrome, were reported to cause maternally inherited gingival fibromatosis and growth hormone deficiency (GHD). Expression of the mutated KCNQ1 with the auxiliary potassium channel subunit KCNE2 was shown to reduce pituitary hormone secretion in functional experiments. Here, we investigated if germline mutations in KCNQ1 and KCNE2 were present in patients with somatotropinomas, which represent a model of growth hormone excess. Design and methods: KCNQ1 and KCNE2 were screened for germline mutations in 53 patients with acromegaly by Sanger sequencing. Effects of the variants were predicted by in silico tools. Results: Only deep intronic and synonymous polymorphisms were detected in KCNQ1. These findings were likely insignificant based on in silico predictions and the variants’ frequencies in the general population. In KCNE2, a heterozygous c.22A>G, p.(Thr8Ala) mutation with unknown significance was found in three patients. It was present in the database controls with a frequency of 0.0038. Conclusions: KCNQ1 or KCNE2 mutations do not appear to account for somatotropinoma formation, although larger patient series are needed to validate the findings.http://www.endocrineconnections.com/content/7/5/645.fullKCNQ1KCNE2growth hormonepituitary adenomaacromegaly |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anna-Pauliina Iivonen Johanna Känsäkoski Atte Karppinen Leena Kivipelto Camilla Schalin-Jäntti Auli Karhu Taneli Raivio |
spellingShingle |
Anna-Pauliina Iivonen Johanna Känsäkoski Atte Karppinen Leena Kivipelto Camilla Schalin-Jäntti Auli Karhu Taneli Raivio Screening for germline KCNQ1 and KCNE2 mutations in a set of somatotropinoma patients Endocrine Connections KCNQ1 KCNE2 growth hormone pituitary adenoma acromegaly |
author_facet |
Anna-Pauliina Iivonen Johanna Känsäkoski Atte Karppinen Leena Kivipelto Camilla Schalin-Jäntti Auli Karhu Taneli Raivio |
author_sort |
Anna-Pauliina Iivonen |
title |
Screening for germline KCNQ1 and KCNE2 mutations in a set of somatotropinoma patients |
title_short |
Screening for germline KCNQ1 and KCNE2 mutations in a set of somatotropinoma patients |
title_full |
Screening for germline KCNQ1 and KCNE2 mutations in a set of somatotropinoma patients |
title_fullStr |
Screening for germline KCNQ1 and KCNE2 mutations in a set of somatotropinoma patients |
title_full_unstemmed |
Screening for germline KCNQ1 and KCNE2 mutations in a set of somatotropinoma patients |
title_sort |
screening for germline kcnq1 and kcne2 mutations in a set of somatotropinoma patients |
publisher |
Bioscientifica |
series |
Endocrine Connections |
issn |
2049-3614 2049-3614 |
publishDate |
2018-04-01 |
description |
Objective: Recently, mutations in KCNQ1, a potassium channel gene usually linked to long QT syndrome, were reported to cause maternally inherited gingival fibromatosis and growth hormone deficiency (GHD). Expression of the mutated KCNQ1 with the auxiliary potassium channel subunit KCNE2 was shown to reduce pituitary hormone secretion in functional experiments. Here, we investigated if germline mutations in KCNQ1 and KCNE2 were present in patients with somatotropinomas, which represent a model of growth hormone excess.
Design and methods: KCNQ1 and KCNE2 were screened for germline mutations in 53 patients with acromegaly by Sanger sequencing. Effects of the variants were predicted by in silico tools.
Results: Only deep intronic and synonymous polymorphisms were detected in KCNQ1. These findings were likely insignificant based on in silico predictions and the variants’ frequencies in the general population. In KCNE2, a heterozygous c.22A>G, p.(Thr8Ala) mutation with unknown significance was found in three patients. It was present in the database controls with a frequency of 0.0038.
Conclusions: KCNQ1 or KCNE2 mutations do not appear to account for somatotropinoma formation, although larger patient series are needed to validate the findings. |
topic |
KCNQ1 KCNE2 growth hormone pituitary adenoma acromegaly |
url |
http://www.endocrineconnections.com/content/7/5/645.full |
work_keys_str_mv |
AT annapauliinaiivonen screeningforgermlinekcnq1andkcne2mutationsinasetofsomatotropinomapatients AT johannakansakoski screeningforgermlinekcnq1andkcne2mutationsinasetofsomatotropinomapatients AT attekarppinen screeningforgermlinekcnq1andkcne2mutationsinasetofsomatotropinomapatients AT leenakivipelto screeningforgermlinekcnq1andkcne2mutationsinasetofsomatotropinomapatients AT camillaschalinjantti screeningforgermlinekcnq1andkcne2mutationsinasetofsomatotropinomapatients AT aulikarhu screeningforgermlinekcnq1andkcne2mutationsinasetofsomatotropinomapatients AT taneliraivio screeningforgermlinekcnq1andkcne2mutationsinasetofsomatotropinomapatients |
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1725615668678623232 |