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A novel heterozygous IGF-1 receptor mutation associated with hypoglycemia
Mutation in the insulin-like growth factor-1 receptor (IGF1R) gene is a rare cause for intrauterine and postnatal growth disorders. Patients identified with IGF1R mutations present with either normal or impaired glucose tolerance. None of the cases described so far showed hypoglycemia. We aimed to i...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Bioscientifica Ltd
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5551424/ https://www.ncbi.nlm.nih.gov/pubmed/28649085 http://dx.doi.org/10.1530/EC-17-0038 |
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author | Solomon-Zemler, R Basel-Vanagaite, L Steier, D Yakar, S Mel, E Phillip, M Bazak, L Bercovich, D Werner, H de Vries, L |
author_facet | Solomon-Zemler, R Basel-Vanagaite, L Steier, D Yakar, S Mel, E Phillip, M Bazak, L Bercovich, D Werner, H de Vries, L |
author_sort | Solomon-Zemler, R |
collection | PubMed |
description | Mutation in the insulin-like growth factor-1 receptor (IGF1R) gene is a rare cause for intrauterine and postnatal growth disorders. Patients identified with IGF1R mutations present with either normal or impaired glucose tolerance. None of the cases described so far showed hypoglycemia. We aimed to identify the genetic basis for small for gestational age, short stature and hypoglycemia over three generations in one family. The proband, a 9-year-old male, presented in infancy with recurrent hypoglycemic episodes, symmetric intrauterine growth retardation and postnatal growth retardation. Blood DNA samples from the patient, his parents, a maternal sister and maternal grandmother underwent Sanger sequencing of the IGF1R gene. Primary skin fibroblast cultures of the patient, his mother and age- and sex-matched control donors were used for gene expression and receptor functional analyses. We found a novel heterozygous mutation (c.94 + 1g > a, D1105E) affecting the splicing site of the IGF1R mRNA in the patient, his mother and his grandmother. Primary fibroblast cultures derived from the patient and his mother showed reduced proliferation and impaired activation of the IGF1R, evident by reduced IGF1R and AKT phosphorylation upon ligand binding. In conclusion, the newly identified heterozygous missense mutation in exon 1 of IGF1R (D1105E) results in impaired IGF1R function and is associated with small for gestational age, microcephaly and abnormal glucose metabolism. Further studies are required to understand the mechanisms by which this mutation leads to hypoglycemia. |
format | Online Article Text |
id | pubmed-5551424 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Bioscientifica Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-55514242017-08-23 A novel heterozygous IGF-1 receptor mutation associated with hypoglycemia Solomon-Zemler, R Basel-Vanagaite, L Steier, D Yakar, S Mel, E Phillip, M Bazak, L Bercovich, D Werner, H de Vries, L Endocr Connect Research Mutation in the insulin-like growth factor-1 receptor (IGF1R) gene is a rare cause for intrauterine and postnatal growth disorders. Patients identified with IGF1R mutations present with either normal or impaired glucose tolerance. None of the cases described so far showed hypoglycemia. We aimed to identify the genetic basis for small for gestational age, short stature and hypoglycemia over three generations in one family. The proband, a 9-year-old male, presented in infancy with recurrent hypoglycemic episodes, symmetric intrauterine growth retardation and postnatal growth retardation. Blood DNA samples from the patient, his parents, a maternal sister and maternal grandmother underwent Sanger sequencing of the IGF1R gene. Primary skin fibroblast cultures of the patient, his mother and age- and sex-matched control donors were used for gene expression and receptor functional analyses. We found a novel heterozygous mutation (c.94 + 1g > a, D1105E) affecting the splicing site of the IGF1R mRNA in the patient, his mother and his grandmother. Primary fibroblast cultures derived from the patient and his mother showed reduced proliferation and impaired activation of the IGF1R, evident by reduced IGF1R and AKT phosphorylation upon ligand binding. In conclusion, the newly identified heterozygous missense mutation in exon 1 of IGF1R (D1105E) results in impaired IGF1R function and is associated with small for gestational age, microcephaly and abnormal glucose metabolism. Further studies are required to understand the mechanisms by which this mutation leads to hypoglycemia. Bioscientifica Ltd 2017-06-22 /pmc/articles/PMC5551424/ /pubmed/28649085 http://dx.doi.org/10.1530/EC-17-0038 Text en © 2017 The authors http://creativecommons.org/licenses/by-nc/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Research Solomon-Zemler, R Basel-Vanagaite, L Steier, D Yakar, S Mel, E Phillip, M Bazak, L Bercovich, D Werner, H de Vries, L A novel heterozygous IGF-1 receptor mutation associated with hypoglycemia |
title | A novel heterozygous IGF-1 receptor mutation associated with hypoglycemia |
title_full | A novel heterozygous IGF-1 receptor mutation associated with hypoglycemia |
title_fullStr | A novel heterozygous IGF-1 receptor mutation associated with hypoglycemia |
title_full_unstemmed | A novel heterozygous IGF-1 receptor mutation associated with hypoglycemia |
title_short | A novel heterozygous IGF-1 receptor mutation associated with hypoglycemia |
title_sort | novel heterozygous igf-1 receptor mutation associated with hypoglycemia |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5551424/ https://www.ncbi.nlm.nih.gov/pubmed/28649085 http://dx.doi.org/10.1530/EC-17-0038 |
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