Two missense mutations in KCNQ1 cause pituitary hormone deficiency and maternally inherited gingival fibromatosis
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Two missense mutations in KCNQ1 cause pituitary hormone deficiency and maternally inherited gingival fibromatosis. / Tommiska, Johanna; Känsäkoski, Johanna; Skibsbye, Lasse; Vaaralahti, Kirsi; Liu, Xiaonan; Lodge, Emily J; Tang, Chuyi; Yuan, Lei; Fagerholm, Rainer; Kanters, Jørgen 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.
In: Nature Communications, Vol. 8, No. 1, 1289, 03.11.2017.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Two missense mutations in KCNQ1 cause pituitary hormone deficiency and maternally inherited gingival fibromatosis
AU - Tommiska, Johanna
AU - Känsäkoski, Johanna
AU - Skibsbye, Lasse
AU - Vaaralahti, Kirsi
AU - Liu, Xiaonan
AU - Lodge, Emily J
AU - Tang, Chuyi
AU - Yuan, Lei
AU - Fagerholm, Rainer
AU - Kanters, Jørgen K
AU - Lahermo, Päivi
AU - Kaunisto, Mari
AU - Keski-Filppula, Riikka
AU - Vuoristo, Sanna
AU - Pulli, Kristiina
AU - Ebeling, Tapani
AU - Valanne, Leena
AU - Sankila, Eeva-Marja
AU - Kivirikko, Sirpa
AU - Lääperi, Mitja
AU - Casoni, Filippo
AU - Giacobini, Paolo
AU - Phan-Hug, Franziska
AU - Buki, Tal
AU - Tena-Sempere, Manuel
AU - Pitteloud, Nelly
AU - Veijola, Riitta
AU - Lipsanen-Nyman, Marita
AU - Kaunisto, Kari
AU - Mollard, Patrice
AU - Andoniadou, Cynthia L
AU - Hirsch, Joel A
AU - Varjosalo, Markku
AU - Jespersen, Thomas
AU - Raivio, Taneli
PY - 2017/11/3
Y1 - 2017/11/3
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 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.
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.
U2 - 10.1038/s41467-017-01429-z
DO - 10.1038/s41467-017-01429-z
M3 - Journal article
C2 - 29097701
VL - 8
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 1289
ER -
ID: 189624441