title: Genotypes and phenotypes of children with SHOX deficiency in France.
abstract: BACKGROUND
  The prevalence of SHOX deficiency in children with short stature (SS) is variable in the literature and various genotypes have been identified.
  
  
  OBJECTIVE
  The aim of our study was to determine the frequency and distribution of SHOX genotypes in a large sample of children with SS in France.
  
  
  METHODS
  Children were enrolled in 38 French pediatric endocrinology centers and were either diagnosed with Leri-Weill syndrome (LWS), idiopathic short stature (ISS), or disproportionate short stature (DSS).
  
  
  METHODS
  SHOX analysis was performed centrally as part of the Genetics and Neuroendocrinology of Short Stature International Study observational study. We compared patients with (SHOX-D) and without SHOX deficiency (non-SHOX-D).
  
  
  RESULTS
  Among the 537 patients tested [58.3% females, mean age 11.0 (4.2) yr], 27.7% had SHOX deficiency (LWS, 48.9%; ISS, 16.9%; DSS, 18.8%). Mean height [-2.3 (0.9) sd score] was similar in SHOX-D and non-SHOX-D patients. The majority of SHOX-D patients with LWS had either a deletion encompassing SHOX or a point mutation (69%), whereas 59% of those with ISS had a deletion downstream of SHOX in the enhancer region. The height of the parents carrying a deletion downstream of SHOX was higher than the height of the parents carrying the other gene anomalies.
  
  
  CONCLUSIONS
  SHOX deletions and point mutations as well as downstream SHOX enhancer deletions were identified in almost one third of the patients tested. An anomaly in this latter region seemed to be linked to a milder phenotype. Although further confirmation is needed, we suggest that the enhancer region should be systematically analyzed in patients suspected of SHOX deficiency.
authors.affiliation: Medical Department, Lilly France, 13 Rue Pagès, 92158 Suresnes Cedex, France. rosilio_myriam@lilly.com
authors.forename: Myriam
authors.initials: M
authors.lastname: Rosilio
authors.forename: Céline
authors.initials: C
authors.lastname: Huber-Lequesne
authors.forename: Hélène
authors.initials: H
authors.lastname: Sapin
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Carel
authors.forename: Werner F
authors.initials: WF
authors.lastname: Blum
authors.forename: Valérie
authors.initials: V
authors.lastname: Cormier-Daire
mesh_terms: D000293:Adolescent; D000465:Algorithms; D001827:Body Height / Q000235:genetics; D002648:Child; D004252:DNA Mutational Analysis; D004392:Dwarfism / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005602:France / Q000453:epidemiology; D056726:Genetic Association Studies; D005838:Genotype; D006130:Growth Disorders / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008069:Lipomatosis, Multiple Symmetrical / Q000150:complications / Q000235:genetics; D008297:Male; D009154:Mutation / Q000502:physiology; D010009:Osteochondrodysplasias / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype; D000074122:Short Stature Homeobox Protein
chemical_list: D018398:Homeodomain Proteins; C106071:SHOX protein, human; D000074122:Short Stature Homeobox Protein