Two missense mutations in KCNQ1 cause pituitary hormone deficiency and maternally inherited gingival fibromatosis.

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_4D6519A1878D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Two missense mutations in KCNQ1 cause pituitary hormone deficiency and maternally inherited gingival fibromatosis.
Journal
Nature communications
Author(s)
Tommiska J., Känsäkoski J., Skibsbye L., Vaaralahti K., Liu X., Lodge E.J., Tang C., Yuan L., Fagerholm R., Kanters J.K., Lahermo P., Kaunisto M., Keski-Filppula R., Vuoristo S., Pulli K., Ebeling T., Valanne L., Sankila E.M., Kivirikko S., Lääperi M., Casoni F., Giacobini P., Phan-Hug F., Buki T., Tena-Sempere M., Pitteloud N., Veijola R., Lipsanen-Nyman M., Kaunisto K., Mollard P., Andoniadou C.L., Hirsch J.A., Varjosalo M., Jespersen T., Raivio T.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
03/11/2017
Peer-reviewed
Oui
Volume
8
Number
1
Pages
1289
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Familial growth hormone deficiency provides an opportunity to identify new genetic causes of short stature. Here we combine linkage analysis with whole-genome resequencing in patients with growth hormone deficiency and maternally inherited gingival fibromatosis. We report that patients from three unrelated families harbor either of two missense mutations, c.347G>T p.(Arg116Leu) or c.1106C>T p.(Pro369Leu), in KCNQ1, a gene previously implicated in the long QT interval syndrome. Kcnq1 is expressed in hypothalamic GHRH neurons and pituitary somatotropes. Co-expressing KCNQ1 with the KCNE2 β-subunit shows that both KCNQ1 mutants increase current levels in patch clamp analyses and are associated with reduced pituitary hormone secretion from AtT-20 cells. In conclusion, our results reveal a role for the KCNQ1 potassium channel in the regulation of human growth, and show that growth hormone deficiency associated with maternally inherited gingival fibromatosis is an allelic disorder with cardiac arrhythmia syndromes caused by KCNQ1 mutations.
Pubmed
Web of science
Open Access
Yes
Create date
16/11/2017 17:22
Last modification date
30/04/2021 6:10
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