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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

Authors :
H. J. van der Kamp
M.J.E. Walenkamp
Alberto M. Pereira
Johannes A. Romijn
Marcel Karperien
J.M. Wit
Sarina G. Kant
Martijn H. Breuning
M. F. Kruithof
H.A. van Duyvenvoorde
Other departments
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

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