Study On The Deficency Of SHOX Gene And The Correlation With Corresponing Phenotypes Of Idiopathic Short Statrue

Objective:To study the deficiency of short stature homeobox containing gene(SHOX) deficiency of idiopathic short stature(ISS) in Chongqing and the relationship between genotypes and its corresponding phenotypes.Methods:1.203 children for short stature at Children'Hospital, Chongqing Medical Univrsity during 2008-7 to 2009-10 were enrolled, included male 109,female 94.2. 70 healthy children for control and 203 patients'fresh whole blood were collected.3. Radiographs of the left forearms and wrists in patients and healthy children were collected to observe their skeletal features。Anthropometric measures were assessed ,including height,sitting height,arm span,forearm length, lower leg length.4.Genomic DNA were extracted from fresh whole blood,then they were amplified with primer pairs designed to span 5 microsatllites of SHOX gene and 5 SHOX exons of all subjects.5.By comparison with controls,microsatellite analysis identified SHOX deletions。 6.Direct sequencing of eoxns identified the patients without SHOX deletions.The seqrences were subsequently compared with SHOX gene sequences in the GeneBank for the potential mutations.7.The comparion of clinical manifestation was made during SHOX-deficient group ,non-SHOX deficient participants in all ISS patients,and the control group with normal height。Results:1.Eleven deletions and a mutation of exon 2 were found in 203 patients with ISS.2.Differences of physical signs during SHOX-deficient group,non-SHOX deficient participants in all ISS patients,and the control group were tested by one-way ANOVA,such as height ,sitting height/height, arm span/height, forearm length/height, lower leg length/height. There were significant difference between SHOX-deficient group and non-SHOX deficient participants,between SHOX-deficient group and the control group:sitting height/height of patients with SHOX defiency increased,and their armspan/height, forearm length/height and lower leg length/height decreased.There were no differences in height bitween two groups(P>0.05).3.In radiographs of the left forearms and wrists of SHOX-deficient group, there were some mild skeletal deformities like Madelung deformity in patients with SHOX deficiency,but the specific relationships between genotypes and bone deformities had not been found yet.Clousions:1.The frequency of SHOX defiency of ISS patients in this research was 5.9%. 2. Sitting height/height of patients with SHOX increased, armspan/height, forearm length/height and lower leg length/height decreased. The results suggested ratio of trunk increasing and mesomelic limb shortening.The decreasing of forearm length/height and lower leg suggested that forearms and lower legs shortened more severly.3. There were some mild and multiple skeletal deformities like Madelung deformity in patients with SHOX deficiency, needed comprehensive analysis.4. The height of short statures patients with SHOX deficiency might be large fluctuations.Most of them had abnormal stature , some were closed to abnormal but in normal range ,others even had normal height in pre-adolescents. This suggested a high degree of phenotypic heterogeneity of SHOX gene deficiency.