When genetic load does not correlate with phenotypic spectrum: Lessons from the GnRH receptor (GNRHR)
Author
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Gianetti, Elena
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Hall, Janet E.
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Au, Margaret G.
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Kaiser, Ursula B.
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Quinton, Richard
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Stewart, Jane A.
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Metzger, Daniel L.
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Pitteloud, Nelly
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Mericq, Verónica
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Merino, Paulina M.
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Levitsky, Lynne L.
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Izatt, Louise
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Lang-Muritano, Mariarosaria
Author
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Fujimoto, Victor Y.
Author
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Dlu
Admission date
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2019-03-11T13:19:40Z
Available date
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2019-03-11T13:19:40Z
Publication date
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2012
Cita de ítem
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Journal of Clinical Endocrinology and Metabolism, Volumen 97, Issue 9, 2018,
Identifier
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0021972X
Identifier
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19457197
Identifier
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10.1210/jc.2012-1264
Identifier
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https://repositorio.uchile.cl/handle/2250/165702
Abstract
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Context: A broad spectrum of GnRH-deficient phenotypes has been identified in individuals with both mono- and biallelic GNRHR mutations. Objective: The objective of the study was to determine the correlation between the severity of the reproductive phenotype(s) and the number and functional severity of rare sequence variants in GNRHR. Subjects: Eight hundred sixty-three probands with different forms of GnRH deficiency, 46 family members and 422 controls were screened for GNRHR mutations. The 70 subjects (32 patients and 38 family members) harboring mutations were divided into four groups (G1-G4) based on the functional severity of the mutations (complete or partial loss of function) and the number of affected alleles (monoallelic or biallelic) with mutations, and these classes were mapped on their clinical phenotypes. Results: The prevalence of heterozygous rare sequence variants in GNRHR was significantly higher in probands vs. controls (P < 0.01). Among the G1-G3 groups (homozygous s