Genetic defects in short stature

Short stature is generally defined as a condition in which the height of an individual is more than 2 standard deviations (SD) below the mean of the corresponding age- and sex-matched population. When none of the traditionally known causes of short stature, i.e. growth hormone (GH) deficiency, GH receptor defect, biologically inactive GH, and several underlying chronic diseases, can be found in a short statured patient, the patient is diagnosed as idiopathic short stature (ISS). Approximately 80% of short children presented in a pediatric clinic is diagnosed as ISS. Genetic testing of children with ISS has revealed several mutations in genes involved in linear growth. These mutations can be a possible cause of the short stature phenotype. Important players in linear growth are several components of the GH-insulin like growth factor-1 (IGF-1) axis and the short stature homeobox gene (SHOX). By identifying genetic defects in these players the diagnosis of short stature can be specified and new, more adjusted therapies can be developed to help these children. This thesis is focused on the genetic defects in signal transducer and activation of transcription 5b (STAT5b), acid labile subunit (ALS), IGF-1, IGF-I receptor (IGF1R) ,and SHOX as encountered in short stature patients