RT Journal Article
T1 Two missense mutations in KCNQ1 cause pituitary hormone deficiency and maternally inherited gingival fibromatosis.
A1 Tommiska, Johanna
A1 Känsäkoski, Johanna
A1 Skibsbye, Lasse
A1 Vaaralahti, Kirsi
A1 Liu, Xiaonan
A1 Lodge, Emily J
A1 Tang, Chuyi
A1 Yuan, Lei
A1 Fagerholm, Rainer
A1 Kanters, Jørgen K
A1 Lahermo, Päivi
A1 Kaunisto, Mari
A1 Keski-Filppula, Riikka
A1 Vuoristo, Sanna
A1 Pulli, Kristiina
A1 Ebeling, Tapani
A1 Valanne, Leena
A1 Sankila, Eeva-Marja
A1 Kivirikko, Sirpa
A1 Lääperi, Mitja
A1 Casoni, Filippo
A1 Giacobini, Paolo
A1 Phan-Hug, Franziska
A1 Buki, Tal
A1 Tena-Sempere, Manuel
A1 Pitteloud, Nelly
A1 Veijola, Riitta
A1 Lipsanen-Nyman, Marita
A1 Kaunisto, Kari
A1 Mollard, Patrice
A1 Andoniadou, Cynthia L
A1 Hirsch, Joel A
A1 Varjosalo, Markku
A1 Jespersen, Thomas
A1 Raivio, Taneli
K1 Adrenocorticotropic hormone
K1 Alleles
K1 Amino acid substitution
K1 Arrhythmias, cardiac
AB 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.
PB Nature Publishing Group
YR 2017
FD 2017-09-14
LK http://hdl.handle.net/10668/11763
UL http://hdl.handle.net/10668/11763
LA en
NO Tommiska J, Känsäkoski J, Skibsbye L, Vaaralahti K, Liu X, Lodge EJ, et al. Two missense mutations in KCNQ1 cause pituitary hormone deficiency and maternally inherited gingival fibromatosis. Nat Commun. 2017 Nov 3;8(1):1289
NO Ms. Lea Puhakka is thanked for skillful technical assistance. Dr. Päivi Miettinen is thanked for commenting on the manuscript. This work was supported by the Academy of Finland (138124 to J.T., 251413 to T.R., 294173 to M.V.), Foundation for Pediatric Research (7495 to T.R.), Sigrid Juselius Foundation (2613 to T.R.), Emil Aaltonen Foundation (2170 to T.R.), Novo Nordisk Foundation (4761 to T.R.), Helsinki University Central Hospital research funds (2010307), Jalmari and Rauha Ahokas Foundation (to J.T.), Paulo Foundation (to J.T.), Danish Council for Independent Research (DFF-1331-00313B to T.J.), Agence Nationale de la Recherche, ANR, France (ANR-14-CE12-0015-01 RoSes and GnRH to P.G.: ANR 12 BSV1 0032 Peri-Pulse to both P.G. and P.M.), Swiss National Science Foundation grants (31003A, 135648 to N.P.), Spanish Ministry of Science (Grant BFI-2014-57581-P to M.T.-S., co-funded with EU funds from FEDER Program), COST grant (Action BM1105), Deutsche Israel Program grant (DFG, to J.A. H.), the King’s Bioscience Institute and the Guy’s and St. Thomas’ Charity Prize Ph.D.Programme in Biomedical and Translational Science (to E.J.L.), and Medical Research Council (MR/L016729/1 to C.L.A.).
DS RISalud
RD Apr 10, 2025