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

Détails

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Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_4D6519A1878D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Two missense mutations in KCNQ1 cause pituitary hormone deficiency and maternally inherited gingival fibromatosis.
Périodique
Nature communications
Auteur(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
Statut éditorial
Publié
Date de publication
03/11/2017
Peer-reviewed
Oui
Volume
8
Numéro
1
Pages
1289
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
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
Oui
Création de la notice
16/11/2017 18:22
Dernière modification de la notice
30/04/2021 7:10
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