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

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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 2017 , ' Two missense mutations in KCNQ1 cause pituitary hormone deficiency and maternally inherited gingival fibromatosis ' , Nature Communications , vol. 8 , 1289 . https://doi.org/10.1038/s41467-017-01429-z

Title: Two missense mutations in KCNQ1 cause pituitary hormone deficiency and maternally inherited gingival fibromatosis
Author: Tommiska, Johanna; Känsäkoski, Johanna; Skibsbye, Lasse; Vaaralahti, Kirsi; Liu, Xiaonan; Lodge, Emily J.; Tang, Chuyi; Yuan, Lei; Fagerholm, Rainer; Kanters, Jorgen K.; Lahermo, Päivi; Kaunisto, Mari; Keski-Filppula, Riikka; Vuoristo, Sanna; Pulli, Kristiina; Ebeling, Tapani; Valanne, Leena; Sankila, Eeva-Marja; Kivirikko, Sirpa; Lääperi, Mitja; Casoni, Filippo; Giacobini, Paolo; Phan-Hug, Franziska; Buki, Tal; Tena-Sempere, Manuel; Pitteloud, Nelly; Veijola, Riitta; Lipsanen-Nyman, Marita; Kaunisto, Kari; Mollard, Patrice; Andoniadou, Cynthia L.; Hirsch, Joel A.; Varjosalo, Markku; Jespersen, Thomas; Raivio, Taneli
Contributor: University of Helsinki, Department of Physiology
University of Helsinki, Raivio Group
University of Helsinki, Department of Physiology
University of Helsinki, Institute of Biotechnology
University of Helsinki, Medicum
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Medicum
University of Helsinki, Medicum
University of Helsinki, Clinicum
University of Helsinki, Clinicum
University of Helsinki, Helsinki University Hospital Area
University of Helsinki, Medicum
University of Helsinki, Clinicum
University of Helsinki, Institute of Biotechnology
University of Helsinki, Medicum
Date: 2017-11-03
Language: eng
Number of pages: 11
Belongs to series: Nature Communications
ISSN: 2041-1723
URI: http://hdl.handle.net/10138/228878
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 beta-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.
Subject: LONG-QT SYNDROME
K+ CHANNEL
ATRIAL-FIBRILLATION
POTASSIUM CHANNELS
STEM-CELLS
GENE
COMPLEX
CALMODULIN
VARIANTS
SUBUNIT
3111 Biomedicine
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