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Two missense mutations in KCNQ1 cause pituitary hormone deficiency and maternally inherited gingival fibromatosis
- Source :
- Nature Communications, 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, no. 1, 1289 . https://doi.org/10.1038/s41467-017-01429-z, Nature Communications, Vol 8, Iss 1, Pp 1-11 (2017), Nature communications, vol. 8, no. 1, pp. 1289
- Publication Year :
- 2017
- Publisher :
- Springer Nature, 2017.
-
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.<br />Growth retardation is most commonly caused by genetic defects in the growth hormone pathway. Here, in families with growth retardation and gingival fibromatosis, the authors identify mutations in the potassium channel gene KCNQ1 that cause electrophysiological aberrations and altered ACTH secretion in vitro.
- Subjects :
- Male
Models, Molecular
0301 basic medicine
endocrine system diseases
General Physics and Astronomy
VARIANTS
Mice
Missense mutation
Protein Interaction Maps
CALMODULIN
lcsh:Science
Child
Multidisciplinary
Human Growth Hormone
KCNE2
Middle Aged
Recombinant Proteins
Pedigree
3. Good health
Child, Preschool
K+ CHANNEL
KCNQ1 Potassium Channel
Female
Maternal Inheritance
medicine.symptom
POTASSIUM CHANNELS
STEM-CELLS
Adult
medicine.medical_specialty
Adolescent
Somatotropic cell
Science
Long QT syndrome
Mutation, Missense
LONG-QT SYNDROME
Adrenocorticotropic hormone
Biology
Short stature
Article
General Biochemistry, Genetics and Molecular Biology
Growth hormone deficiency
Young Adult
03 medical and health sciences
Adrenocorticotropic Hormone
Genetic linkage
Internal medicine
medicine
Animals
Humans
Alleles
Fibromatosis, Gingival
COMPLEX
urogenital system
Arrhythmias, Cardiac
General Chemistry
medicine.disease
GENE
030104 developmental biology
Endocrinology
Amino Acid Substitution
ATRIAL-FIBRILLATION
SUBUNIT
biology.protein
lcsh:Q
3111 Biomedicine
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Nature Communications, 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, no. 1, 1289 . https://doi.org/10.1038/s41467-017-01429-z, Nature Communications, Vol 8, Iss 1, Pp 1-11 (2017), Nature communications, vol. 8, no. 1, pp. 1289
- Accession number :
- edsair.doi.dedup.....91f65b757cd3eec6b9407f896b92ee41