Screening for germline KCNQ1 and KCNE2 mutations in a set of somatotropinoma patients.

Abstract:

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.

journal_name

Endocr Connect

journal_title

Endocrine connections

authors

Iivonen AP,Känsäkoski J,Karppinen A,Kivipelto L,Schalin-Jäntti C,Karhu A,Raivio T

doi

10.1530/EC-18-0123

subject

Has Abstract

pub_date

2018-05-01 00:00:00

pages

645-652

issue

5

issn

2049-3614

pii

EC-18-0123

journal_volume

7

pub_type

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