دورية أكاديمية
A homozygous point mutation in the GH1 promoter (c.-223C>T) leads to reduced GH1 expression in siblings with isolated GH deficiency (IGHD).
| العنوان: | A homozygous point mutation in the GH1 promoter (c.-223C>T) leads to reduced GH1 expression in siblings with isolated GH deficiency (IGHD). |
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| المؤلفون: | Madeira JL; Unidade de Endocrinologia do DesenvolvimentoLaboratório de Hormônios e Genética Molecular LIM/42., Jorge AA; Unidade de Endocrinologia do DesenvolvimentoLaboratório de Hormônios e Genética Molecular LIM/42 Unidade de Endocrinologia-Genética - LIM/25Disciplina de Endocrinologia da Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil., Martin RM; Unidade de Endocrinologia do DesenvolvimentoLaboratório de Hormônios e Genética Molecular LIM/42., Montenegro LR; Unidade de Endocrinologia do DesenvolvimentoLaboratório de Hormônios e Genética Molecular LIM/42., Franca MM; Unidade de Endocrinologia do DesenvolvimentoLaboratório de Hormônios e Genética Molecular LIM/42., Costalonga EF; Unidade de Endocrinologia do DesenvolvimentoLaboratório de Hormônios e Genética Molecular LIM/42., Correa FA; Unidade de Endocrinologia do DesenvolvimentoLaboratório de Hormônios e Genética Molecular LIM/42., Otto AP; Unidade de Endocrinologia do DesenvolvimentoLaboratório de Hormônios e Genética Molecular LIM/42., Arnhold IJ; Unidade de Endocrinologia do DesenvolvimentoLaboratório de Hormônios e Genética Molecular LIM/42., Freitas HS; Laboratório de Metabolismo e Endocrinologia do Departamento de Fisiologia e Biofísica do Instituto de Ciências Biomédicas da Universidade de São Paulo (ICB-USP)São Paulo, Brazil., Machado UF; Laboratório de Metabolismo e Endocrinologia do Departamento de Fisiologia e Biofísica do Instituto de Ciências Biomédicas da Universidade de São Paulo (ICB-USP)São Paulo, Brazil., Mendonca BB; Unidade de Endocrinologia do DesenvolvimentoLaboratório de Hormônios e Genética Molecular LIM/42., Carvalho LR; Unidade de Endocrinologia do DesenvolvimentoLaboratório de Hormônios e Genética Molecular LIM/42 lucianic@gmail.com. |
| المصدر: | European journal of endocrinology [Eur J Endocrinol] 2016 Aug; Vol. 175 (2), pp. K7-K15. Date of Electronic Publication: 2016 Jun 01. |
| نوع المنشور: | Case Reports; Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 9423848 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1479-683X (Electronic) Linking ISSN: 08044643 NLM ISO Abbreviation: Eur J Endocrinol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2023- : Oxford : Oxford University Press Original Publication: Oslo, Norway : Scandinavian University Press, c1994- |
| مواضيع طبية MeSH: | Point Mutation* , Promoter Regions, Genetic*, Dwarfism, Pituitary/*genetics , Human Growth Hormone/*genetics, Adult ; Alleles ; Female ; Genotype ; Homozygote ; Humans ; Male ; Pedigree ; Siblings |
| مستخلص: | Context: Mutations in the GH1 promoter are a rare cause of isolated growth hormone deficiency (IGHD). Objective: To identify the molecular aetiology of a family with IGHD. Design: DNA sequencing, electromobility shift (EMSA) and luciferase reporter assays. Setting: University Hospital. Patients: Three siblings (2M) born to consanguineous parents presented with IGHD with normal pituitary on MRI. Methods: The GH1 proximal promoter, locus control region, five exons and four introns as well as GHRHR gene were sequenced in genomic DNA by Sanger method. DNA-protein interaction was evaluated by EMSA in nuclear extracts of GH3 pituitary cells. Dual-luciferase reporter assays were performed in cells transiently transfected with plasmids containing four different combinations of GH1 allelic variants (AV). Results: The patients harboured two homozygous variants (c.-185T>C and c.-223C>T) in the GH1 promoter within a highly conserved region and predicted binding sites for POU1F1/SP1 and SP1 respectively. The parents and brother were carriers and these variants were absent in 100 controls. EMSA demonstrated absent binding of GH3 nuclear extract to the c.-223C>T variant and normal binding of both POU1F1 protein and GH3 nuclear extract to the c.-185T>C variant. In contrast to GH1 promoter with AV only at c.-185, the GH1 promoter containing the AV only at c.-223 and at both positions drove significantly less expression of luciferase compared with the promoter containing either positions wild type in luciferase reporter assays. Conclusion: To our knowledge, c.-223C>T is the first homozygous point mutation in the GH1 promoter that leads to short stature due to IGHD. (© 2016 European Society of Endocrinology.) |
| المشرفين على المادة: | 12629-01-5 (Human Growth Hormone) |
| تواريخ الأحداث: | Date Created: 20160603 Date Completed: 20170206 Latest Revision: 20170206 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1530/EJE-15-0149 |
| PMID: | 27252485 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1479-683X |
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| DOI: | 10.1530/EJE-15-0149 |