eprintid: 10080724 rev_number: 18 eprint_status: archive userid: 608 dir: disk0/10/08/07/24 datestamp: 2019-08-30 12:02:55 lastmod: 2021-12-13 03:00:51 status_changed: 2019-08-30 12:02:55 type: article metadata_visibility: show creators_name: Tommiska, J creators_name: Kansakoski, J creators_name: Skibsbye, L creators_name: Vaaralahti, K creators_name: Liu, X creators_name: Lodge, EJ creators_name: Tang, C creators_name: Yuan, L creators_name: Fagerholm, R creators_name: Kanters, JK creators_name: Lahermo, P creators_name: Kaunisto, M creators_name: Keski-Filppula, R creators_name: Vuoristo, S creators_name: Pulli, K creators_name: Ebeling, T creators_name: Valanne, L creators_name: Sankila, E-M creators_name: Kivirikko, S creators_name: Laaperi, M creators_name: Casoni, F creators_name: Giacobini, P creators_name: Phan-Hug, F creators_name: Buki, T creators_name: Tena-Sempere, M creators_name: Pitteloud, N creators_name: Veijola, R creators_name: Lipsanen-Nyman, M creators_name: Kaunisto, K creators_name: Mollard, P creators_name: Andoniadou, CL creators_name: Hirsch, JA creators_name: Varjosalo, M creators_name: Jespersen, T creators_name: Raivio, T title: Two missense mutations in KCNQ1 cause pituitary hormone deficiency and maternally inherited gingival fibromatosis ispublished: pub divisions: UCL divisions: B02 divisions: D13 divisions: G22 note: 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/. 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. date: 2017-11-03 date_type: published publisher: NATURE PUBLISHING GROUP official_url: https://doi.org/10.1038/s41467-017-01429-z oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1509641 doi: 10.1038/s41467-017-01429-z lyricists_name: Lodge, Emily lyricists_id: EJLOD08 actors_name: Barczynska, Patrycja actors_id: PBARC91 actors_role: owner full_text_status: public publication: Nature Communications volume: 8 article_number: 1289 pages: 11 issn: 2041-1723 citation: Tommiska, J; Kansakoski, J; Skibsbye, L; Vaaralahti, K; Liu, X; Lodge, EJ; Tang, C; ... Raivio, T; + view all <#> Tommiska, J; Kansakoski, J; Skibsbye, L; Vaaralahti, K; Liu, X; Lodge, EJ; Tang, C; Yuan, L; Fagerholm, R; Kanters, JK; Lahermo, P; Kaunisto, M; Keski-Filppula, R; Vuoristo, S; Pulli, K; Ebeling, T; Valanne, L; Sankila, E-M; Kivirikko, S; Laaperi, 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, CL; Hirsch, JA; Varjosalo, M; Jespersen, T; Raivio, T; - view fewer <#> (2017) Two missense mutations in KCNQ1 cause pituitary hormone deficiency and maternally inherited gingival fibromatosis. Nature Communications , 8 , Article 1289. 10.1038/s41467-017-01429-z <https://doi.org/10.1038/s41467-017-01429-z>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10080724/1/s41467-017-01429-z.pdf