Studies On The Growth Hormone Receptor Exon3Polymorphism And Response To Growth Hormone Therapy In Turner Syndrome

Object:To study the distribution of growth hormone receptor (GHR) Exon3polymorphism in Chinese Turner syndrome patient, to explore the relationship between the polymorphism and the Recombinant human growth hormone (GH) treatment efficacyMaterial and methods:This was a retrospective study of31Turner syndrome, GH had been administered to the31patient at least one year, nine of which has been treated for two years, the change of height standard deviation (ΔHt-SDS), the change of growth rate (ΔGV) and height change (ΔHt) as indicators to measure GH treatment efficacy, Genomic DNA was isolated from peripheral blood lymphocytes, The GHR Exon3polymorphism was detected by PCR assay, Hardy-Weinberg genetic equilibrium method to test the theoretical value of each genotype, the data was analysed by the SPSS12.0software(t test, Chi-square test, pearson correlation analysis and multiple linear regression analysis)Results:(1) the distribution frequency of the fl/fl-GHR, fl/d3-GHR d3/d3-GHR in this study were41.9%,45.2%and12.9%, respectively, there was no difference.(2) Before the growth hormone therapy and after1year of treatment, the growth rate (GV,2.94±0.89vs7.36±1.34) and Height SD Score (Ht-SDS,-3.47±1.33vs-2.78±1.24) of the31Turner syndrome children are significantly different (p<0.05)(3) In the nine Turner syndrome patient who were treated for two years, the growth velocity of the year before treatment, the first year treatment and the second year treatment was (3.39±0.56vs7.98±0.73vs7.07±0.98)respectively, There were statistical significance between the them(p<0.05). The Ht-SDS of the time begin to treatment, the first year and the second year treatment was (3.48±1.51vs2.48±1.25vs1.01±1.02) respectively, there was no significant difference between the first year treatment and the time begin to treatment(p>0.05), there was significant difference between the second year treatment and the first year as well as the time begin to treatment(p<0.05).(4)There were no difference in Δ GV;ΔHt;ΔHt-SDS and rhGH dose between the three group(fl/fl-GHR vs fl/d3-GHR vsd3/d3-GHR) at the first year treatment(p>0.05).(5) After two years treatment,there were no difference the second year ΔGV; total two year ΔHt and the two year ΔGV between the fl/fl-GHR group and(fl/d3-GHR+d3/d3-GHR) group(p>0.05).(6) According to the karyotype,the31patient were devided into three group:45x karyotype group, chimeric karyotype group and structural aberrations karyotype group, the ΔHt-SDS of the three group were0.54±0.35SDS、0.86±0.44SDS and0.56±2.44SDS,the ΔHt-SDS was significant difference between the45x karyotype group and chimeric karyotype group(p<0.05),there were no significant difference between the other two group. there were no difference in ΔGV and ΔHt between the three group.(7)In the patient who were treated for one year, according the pearson analysis, the ΔHt-SDS was correlation with start age, Ht-SDS, BMI and GV before treatment (p<0.05), ΔHt-SDS wasn’t correlation with BA, GHR genotype,rhGH dose (p>0.05). there was no correlation between the ΔGV and the parameters. according to Linear regression, the ΔHt-SDS was correlation with start age, GV(p<0.05), regression coefficient was-0.096and0.217,respectively.(9) In the patient who were treated for two year, according to the pearson analysis, Δ Ht-SDS wasn’t correlatGVo,vsBMI,vs BA, vs growth hormone dose were greater than0.05, The p value of pearson analysis in ΔGV vs on with GVo,, BMI, BA, and rhGH dose(p>0.05)Conclusion:In this study, the distribution of GHR exon3deletion polymorphism frequency in Chinese Turner syndrome are different from foreign Turner syndrome, which indicated that the GHR genotype distribution may have ethnic variations, There was no significant correlation between the GHR Exon3polymorphism and the effect of GH treatment in Chinese Turner syndrome, Karyotype may be associated with the efficacy of GH therapy, The efficacy of growth hormone was negatively correlated with initial treatment age and was positively correlated with untreated growth velocity. Objective:analysis the clinical characteristics and detect the PTPN11gene in4clinically suspected Noonan syndrome patients.Methods:Summary clinical manifestations of4cases who were suspected Noonan syndrome, Analysis of the karyotype, we select the PTPN11gene for the purpose gene,PTPN11gene hotspot mutations in exons (2,3,4,7,8,12,13) was amplified by PCR, the PCR product was sequenced by ABI3730sequence analyzer to obtain the peak of FIG. DNA Baser sequence assembly software analysis sequencing results showed that the mutation site, and finally in the human Genome mutation Database (HGMD) View the mutation site is the causative mutation.Results:Four infants have short stature, Down-slanting palpebral fissures, ptosis, orbital hypertelorism, Cubitus valgus and congenital heart disease, chromosome karyotypes were normal,2patients PTPN11gene sequencing were normal,2patients in the presence of disease-causing mutations in the PTPN11gene, in patient A, The A�'G transition at position1510in PTPN11Exon13, predicting an met504val substitution. in patient B, The A�'G transition at position236in PTPN11Exon3, predicting an Gln79Arg substitution, Two mutations are reported pathogenic mutations of the Noonan syndrome.Conclusion:The clinical feature of Turner syndrome,GHARGE syndrome, Costello syndrome similar to Noonan syndrome, PTPN11gene is the most common disease-causing gene in Noonan syndrome, in children who was suspected with Noonan syndrome can carry on the PTPN11gene testing, Noonan syndrome is a genetically heterogeneous disease, negative result does not rule out Noonan syndrome.