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Screening a large pediatric cohort with GH deficiency for mutations in genes regulating pituitary development and GH secretion: Frequencies, phenotypes and growth outcomesResearch in context

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العنوان: Screening a large pediatric cohort with GH deficiency for mutations in genes regulating pituitary development and GH secretion: Frequencies, phenotypes and growth outcomesResearch in context
المؤلفون: Werner F. Blum, Jürgen Klammt, Serge Amselem, Heike M. Pfäffle, Marie Legendre, Marie-Laure Sobrier, Marie-Pierre Luton, Christopher J. Child, Christine Jones, Alan G. Zimmermann, Charmian A. Quigley, Gordon B. Cutler, Jr, Cheri L. Deal, Jan Lebl, Ron G. Rosenfeld, John S. Parks, Roland W. Pfäffle
المصدر: EBioMedicine, Vol 36, Iss , Pp 390-400 (2018)
بيانات النشر: Elsevier, 2018.
سنة النشر: 2018
المجموعة: LCC:Medicine
LCC:Medicine (General)
مصطلحات موضوعية: Medicine, Medicine (General), R5-920
الوصف: Background: Pituitary development and GH secretion are orchestrated by multiple genes including GH1, GHRHR, GLI2, HESX1, LHX3, LHX4, PROP1, POU1F1, and SOX3. We aimed to assess their mutation frequency and clinical relevance in children with severe GH deficiency (GHD). Methods: The Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS; Clinical Trial Registry Number: NCT01088412) was a prospective, open-label, observational research program for pediatric patients receiving GH treatment, conducted in 30 countries between 1999 and 2015. The study included a sub-study to investigate mutations in the genes listed above. PCR products from genomic blood cell DNA were analyzed by Sanger sequencing. DNA variants were classified as pathogenic according to the recommendations of the American College of Medical Genetics and Genomics. Demographic, auxologic, and endocrine data at baseline and during GH treatment were documented and related to the genotyping results. Findings: The analysis comprised 917 patients. In 92 patients (10%) 33 mutations were found, 16 previously described and 17 novel (52%). Mutation carriers were significantly younger, shorter, and more slowly growing than non-carriers. In general, their peak values in GH stimulation tests were very low; however, in 15/77 (20%) patients with GH1, PROP1, and SOX3 mutations they were only moderately diminished (3-6 μg/L). Two patients with a GH1 mutation developed TSH deficiency and one ADH deficiency. Using logistic multi-regression analysis, significant indicators of a mutation were combined pituitary hormone deficiency, greater patient-parent height difference (SDS), low GH peak, and young age. Final height SDS gain in mutation carriers (mean ± SD 3.4 ± 1.4) was greater than in non-carriers (2.0 ± 1.4; P
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2352-3964
Relation: http://www.sciencedirect.com/science/article/pii/S2352396418303840; https://doaj.org/toc/2352-3964
DOI: 10.1016/j.ebiom.2018.09.026
URL الوصول: https://doaj.org/article/eb38d45a2af84fb1a420e9f01ae4ca4c
رقم الأكسشن: edsdoj.b38d45a2af84fb1a420e9f01ae4ca4c
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:23523964
DOI:10.1016/j.ebiom.2018.09.026