title: 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.
abstract: 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.
authors.affiliation: Departments of Pediatrics, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, United Kingdom.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Okubo
authors.forename: Ken
authors.initials: K
authors.lastname: Siddle
authors.forename: Helen
authors.initials: H
authors.lastname: Firth
authors.forename: Steve
authors.initials: S
authors.lastname: O'Rahilly
authors.forename: Louise C
authors.initials: LC
authors.lastname: Wilson
authors.forename: Lionel
authors.initials: L
authors.lastname: Willatt
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Fukushima
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Takahashi
authors.forename: Clive J
authors.initials: CJ
authors.lastname: Petry
authors.forename: Tero
authors.initials: T
authors.lastname: Saukkonen
authors.forename: Richard
authors.initials: R
authors.lastname: Stanhope
authors.forename: David B
authors.initials: DB
authors.lastname: Dunger
mesh_terms: D001827:Body Height; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D020732:Cytogenetic Analysis; D005260:Female; D005347:Fibroblasts / Q000473:pathology*; D018628:Gene Dosage; D006130:Growth Disorders / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010766:Phosphorylation; D017526:Receptor, IGF Type 1 / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012867:Skin / Q000473:pathology*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D014443:Tyrosine; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1