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Growth failure in a child showing characteristics of Seckel syndrome: possible effects of IGF‐I and endogenous IGFBP‐3
Author(s) -
Schmidt A.,
Chakravarty A.,
Brommer E.,
Fenne B. D.,
Siebler T.,
De Meyts P.,
Kiess W.
Publication year - 2002
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1046/j.1365-2265.2002.01590.x
Subject(s) - endocrinology , short stature , medicine , radioimmunoassay , receptor , western blot , growth factor , biology , messenger rna , endogeny , gene , blot , growth retardation , insulin like growth factor binding protein , insulin like growth factor , genetics , pregnancy
Summary Seckel syndrome is an autosomal‐recessive disorder with a frequency of less than 1/10 000 births in which there are multiple malformations including severe short stature. We report on a patient with Seckel syndrome with a current body height of −7·5 SDS. Laboratory investigations at the age of 19 months revealed high levels of IGF‐I, IGF‐II and IGFBP‐3. These data suggested the existence of IGF‐I resistance possibly caused by impairment of the IGF‐I receptor (IGF‐IR) or altered IGFBPs. The purpose of this investigation was to examine whether the growth retardation in a Seckel syndrome patient is related to an alteration in the IGF system. Analysis of IGF‐IR mRNA of patient's and control fibroblasts by solution hybridization/RNase protection assay did not show differences of IGF‐IR transcript expression or size. Affinity crosslinking studies using [ 125 I]‐IGF‐I showed normal‐sized IGF‐IR–ligand complexes. Mutation analysis of the complete coding regions of the IGF‐I and IGF‐IR genes showed no evidence of genetic alterations. Ligand blot analysis of IGFBPs secreted by the patient's fibroblasts showed stronger signals than control cells. Quantitative measurement of IGFBP‐3 in cell‐conditioned media was performed by radioimmunoassay (RIA) and revealed a sixfold increase when compared to control fibroblasts. We conclude that in this patient with Seckel syndrome and severe growth impairment IGF‐I resistance is possibly related to altered production of IGFBP‐3.