%0 Journal Article
%@ 2041-1723
%A Tommiska, J
%A Kansakoski, J
%A Skibsbye, L
%A Vaaralahti, K
%A Liu, X
%A Lodge, EJ
%A Tang, C
%A Yuan, L
%A Fagerholm, R
%A Kanters, JK
%A Lahermo, P
%A Kaunisto, M
%A Keski-Filppula, R
%A Vuoristo, S
%A Pulli, K
%A Ebeling, T
%A Valanne, L
%A Sankila, E-M
%A Kivirikko, S
%A Laaperi, M
%A Casoni, F
%A Giacobini, P
%A Phan-Hug, F
%A Buki, T
%A Tena-Sempere, M
%A Pitteloud, N
%A Veijola, R
%A Lipsanen-Nyman, M
%A Kaunisto, K
%A Mollard, P
%A Andoniadou, CL
%A Hirsch, JA
%A Varjosalo, M
%A Jespersen, T
%A Raivio, T
%D 2017
%F discovery:10080724
%I NATURE PUBLISHING GROUP
%J Nature Communications
%T Two missense mutations in KCNQ1 cause pituitary hormone deficiency and maternally inherited gingival fibromatosis
%U https://discovery.ucl.ac.uk/id/eprint/10080724/
%V 8
%X 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.
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