Back to Search
Start Over
A variable degree of intrauterine and postnatal growth retardation in a family with a missense mutation in the insulin-like growth factor I receptor
A variable degree of intrauterine and postnatal growth retardation in a family with a missense mutation in the insulin-like growth factor I receptor
- Source :
- Journal of clinical endocrinology and metabolism, 91(8), 3062-3070. The Endocrine Society
- Publication Year :
- 2006
-
Abstract
- The type 1 IGF-I receptor (IGF1R) mediates the biological functions of IGF-I. Binding of IGF-I to the IGF1R results in autophosphorylation of the intracellular beta-subunit and activation of intracellular signaling. The objective of this study was to evaluate the functional characteristics of a novel IGF1R mutation and describe the phenotypic features of two patients with this mutation. The study was performed in a university hospital. We describe a 35-yr-old female with mild intrauterine growth failure, progressive postnatal growth retardation, severe failure to thrive, and microcephaly. Her daughter was born with severe intrauterine growth retardation and also showed postnatal failure to thrive and microcephaly. We found a heterozygous G3148-->A nucleotide substitution in the IGF1R gene, changing a negatively charged glutamic acid at position 1050 into a positively charged lysine residue (E1050K). E1050 is a conserved residue in the intracellular kinase domain. Dermal fibroblasts of the mother showed normal binding of iodinated IGF-I, but autophosphorylation and activation of downstream signaling cascades upon challenging with IGF-I was markedly reduced. Consequently, the maximal [(3)H]thymidine incorporation upon challenge with a dose range of IGF-I was reduced compared with a panel of control cells (3.65 +/- 1.79-fold vs. 6.75 +/- 4.7-fold stimulation; P
- Subjects :
- Adult
Heterozygote
medicine.medical_specialty
Microcephaly
DNA, Complementary
Endocrinology, Diabetes and Metabolism
DNA Mutational Analysis
Clinical Biochemistry
Mutation, Missense
Glutamic Acid
Context (language use)
Biology
medicine.disease_cause
Polymerase Chain Reaction
Biochemistry
Receptor, IGF Type 1
Endocrinology
Bone Density
Internal medicine
medicine
Humans
Missense mutation
Insulin-Like Growth Factor I
Phosphorylation
Growth Disorders
Insulin-like growth factor 1 receptor
Mutation
Fetal Growth Retardation
Base Sequence
Lysine
Biochemistry (medical)
Autophosphorylation
Infant
Sequence Analysis, DNA
Fibroblasts
medicine.disease
Body Height
Failure to Thrive
body regions
Failure to thrive
Severe intrauterine growth retardation
Female
medicine.symptom
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 0021972X
- Volume :
- 91
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Journal of clinical endocrinology and metabolism
- Accession number :
- edsair.doi.dedup.....f75475de77d1615347c2bdcc9e1ecb9e
- Full Text :
- https://doi.org/10.1210/jc.2005-1597