Cell proliferation activities on skin fibroblasts from a short child with absence of one copy of the type 1 insulin-like growth factor receptor (IGF1R) gene and a tall child with three copies of the IGF1R gene

被引:94
作者
Okubo, Y
Siddle, K
Firth, H
O'Rahilly, S
Wilson, LC
Willatt, L
Fukushima, T
Takahashi, SI
Petry, CJ
Saukkonen, T
Stanhope, R
Dunger, DB
机构
[1] Univ Cambridge, Addenbrookes Hosp, Dept Pediat, Cambridge CB2 2QQ, England
[2] Univ Cambridge, Addenbrookes Hosp, Dept Clin Biochem, Cambridge CB2 2QQ, England
[3] Univ Cambridge, Addenbrookes Hosp, Dept Med Genet, Cambridge CB2 2QQ, England
[4] Univ Tokyo, Grad Sch Agr & Life Sci, Clin & Mol Genet Unit, Tokyo 1138657, Japan
[5] Univ Tokyo, Grad Sch Agr & Life Sci, Dept Anim Resource Sci & Appl Biol Chem, Tokyo 1138657, Japan
[6] Inst Child Hlth, Biochem Endocrinol & Metab Unit, London WC1N 1EH, England
[7] Great Ormond St Hosp Sick Children, London WC1N 1EH, England
关键词
D O I
10.1210/jc.2002-021080
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The type 1 IGF receptor (IGF1R) is required for normal embryonic and postnatal growth. The aim of this study was to determine whether we could detect abnormal IGF1R function in skin fibroblasts from children with an abnormal copy number of the IGF1R gene. We report two children with altered copy number of the IGF1R gene who presented with abnormal growth. Case 1 is a girl with intrauterine growth retardation, postnatal growth failure, and recurrent hypoglycemia. Pituitary function tests were normal. Routine karyotype analysis identified a deletion on 15q26.2, and a fluorescence in situ hybridization study using IGF1R probes showed only a single IGF1R gene. Case 2 was large for gestational age, with birth weight and length at or above 97th percentile, and showed rapid early postnatal growth. He was found to have a recombinant chromosome 15 containing a partial duplication at 15q (q25-qter). A fluorescence in situ hybridization study using the same probes showed three copies of the IGF1R gene. In a mitochondrial activity assay, skin fibroblasts from the subject with only one copy of IGF1R showed slower growth, whereas cells from the subject with three copies of IGF1R showed accelerated growth compared with controls. IGF1R phosphorylation, as assessed by Western blot, and IGF1R binding studies were decreased compared with controls in the child with one copy of the IGF1R and increased in the child with three copies of the gene. Our data are consistent with the concept that IGF1R gene copy number is of functional and clinical importance in humans.
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页码:5981 / 5988
页数:8
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