TY  - JOUR
N1  - This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article?s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article?s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
TI  - Two missense mutations in KCNQ1 cause pituitary hormone deficiency and maternally inherited gingival fibromatosis
AV  - public
Y1  - 2017/11/03/
VL  - 8
EP  - 11
JF  - Nature Communications
A1  - Tommiska, J
A1  - Kansakoski, J
A1  - Skibsbye, L
A1  - Vaaralahti, K
A1  - Liu, X
A1  - Lodge, EJ
A1  - Tang, C
A1  - Yuan, L
A1  - Fagerholm, R
A1  - Kanters, JK
A1  - Lahermo, P
A1  - Kaunisto, M
A1  - Keski-Filppula, R
A1  - Vuoristo, S
A1  - Pulli, K
A1  - Ebeling, T
A1  - Valanne, L
A1  - Sankila, E-M
A1  - Kivirikko, S
A1  - Laaperi, M
A1  - Casoni, F
A1  - Giacobini, P
A1  - Phan-Hug, F
A1  - Buki, T
A1  - Tena-Sempere, M
A1  - Pitteloud, N
A1  - Veijola, R
A1  - Lipsanen-Nyman, M
A1  - Kaunisto, K
A1  - Mollard, P
A1  - Andoniadou, CL
A1  - Hirsch, JA
A1  - Varjosalo, M
A1  - Jespersen, T
A1  - Raivio, T
N2  - 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 ?-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.
ID  - discovery10080724
UR  - https://doi.org/10.1038/s41467-017-01429-z
PB  - NATURE PUBLISHING GROUP
SN  - 2041-1723
ER  -