title: IGF1, IGF1R and SHOX mutation analysis in short children born small for gestational age and short children with normal birth size (idiopathic short stature).
abstract: OBJECTIVE
  Because the criteria for genetic screening of short children are unknown, we performed genetic analysis of 199 short children born small for gestational age (SGA) or with normal birth size (idiopathic short stature, ISS).
  
  
  METHODS
  After selection with a modified scoring system for SHOX and a novel score for IGF1 and IGF1R defects, direct sequencing and multiplex ligation-dependent probe amplification (MLPA) was performed for SHOX and IGF1R in selected patients, and confirmed by SNP array analysis.
  
  
  RESULTS
  In 6 children, gene variants were identified in SHOX, its adjacent pseudoautosomal region (PAR) and IGF1R: a SHOX mutation, terminal 15q deletion, a SHOX and IGF1R defect, a deletion of the Xp22.3 PAR region, and two patients with duplications in the Xp22.3 PAR region. In a seventh patient, steroid sulfatase deficiency was detected because a probe for STS was used as control; this syndrome has not been associated with short stature before.
  
  
  CONCLUSIONS
  A selection process using clinical scores for SHOX, IGF1 and IGF1R defects followed by genetic testing with MLPA and direct sequencing led to the detection of a SHOX or IGF1R genetic variant in 6% of short children.
authors.affiliation: University Children's Hospital, Tuebingen, Germany.
authors.forename: Janina
authors.initials: J
authors.lastname: Caliebe
authors.forename: Sander
authors.initials: S
authors.lastname: Broekman
authors.forename: Merel
authors.initials: M
authors.lastname: Boogaard
authors.forename: Cathy A J
authors.initials: CA
authors.lastname: Bosch
authors.forename: Claudia A L
authors.initials: CA
authors.lastname: Ruivenkamp
authors.forename: Wilma
authors.initials: W
authors.lastname: Oostdijk
authors.forename: S G
authors.initials: SG
authors.lastname: Kant
authors.forename: Gerhard
authors.initials: G
authors.lastname: Binder
authors.forename: Michael B
authors.initials: MB
authors.lastname: Ranke
authors.forename: Jan M
authors.initials: JM
authors.lastname: Wit
authors.forename: Monique
authors.initials: M
authors.lastname: Losekoot
mesh_terms: D015331:Cohort Studies; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics* / Q000378:metabolism; D020440:Gene Duplication; D056726:Genetic Association Studies; D005858:Germany; D006130:Growth Disorders / Q000235:genetics* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016114:Ichthyosis, X-Linked / Q000235:genetics / Q000378:metabolism; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011544:Pseudogenes; D017526:Receptor, IGF Type 1 / Q000235:genetics* / Q000378:metabolism; D017384:Sequence Deletion; D000074122:Short Stature Homeobox Protein
chemical_list: D018398:Homeodomain Proteins; C106071:SHOX protein, human; D000074122:Short Stature Homeobox Protein; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1