A novel heterozygous IGF-1 receptor mutation associated with hypoglycemia
| Autor: | Dani Bercovich, Shoshana Yakar, D. Steier, E. Mel, R. Solomon-Zemler, L. Bazak, Lina Basel-Vanagaite, Haim Werner, Moshe Phillip, L. de Vries |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Proband medicine.medical_specialty Microcephaly Endocrinology Diabetes and Metabolism insulin-like growth factor-1 (IGF-1) Hypoglycemia lcsh:Diseases of the endocrine glands. Clinical endocrinology Short stature Impaired glucose tolerance 03 medical and health sciences Endocrinology IUGR Internal medicine Internal Medicine medicine Missense mutation Insulin-like growth factor 1 receptor SGA IGF-1 receptor (IGF1R) lcsh:RC648-665 business.industry Research medicine.disease body regions hypoglycemia 030104 developmental biology Small for gestational age medicine.symptom business |
| Zdroj: | Endocrine Connections, Vol 6, Iss 6, Pp 395-403 (2017) Endocrine Connections |
| ISSN: | 2049-3614 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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