Study On The Defect Of SHOX Gene And Its Conserved Noncoding DNA Elements And The Relationships With Phenotypes And X-ray Of Idiopathic Short Stature

Objective：Study on the defect of SHOX gene and its conserved noncodingelements (CNE) and the relationships with phenotypes and x-ray of patientsof idiopathic short stature(ISS).Methods：Using sequencing and microsatellites analysed the variations inCNE and the upstream and downstream of SHOX gene in501cases;then,investigated the relationships with phenotypes and x-ray of patientswith ISS of normal gene and normal controls.Results：1. In all of the cases, the group of CNE abnormity together accounted for36cases(7.19%), and male had20cases,female had16cases: DXYS10083deletion accounted for6cases, DXYS10087deletion accounted for8cases,DXYS10096deletion accounted for9cases, CNE9deletion accounted for2cases, DXYS233deletion accounted for3cases, DXYS234deletionaccounted for6cases, DXYS233/DXYS10087and DXYS234/DXYS10096common deletions respectively accounted for1case.2. The group of SHOX gene abnormity together accounted for22 cases(4.39%), and male had12cases,female had10cases.CA-SHOXdeletion accounted for8cases, DXYS10092deletion accounted for5cases,DXYS10093deletion accounted for4cases, exon of SHOX mutationaccounted for3cases; CA-SHOX/DXYS10083,CA-SHOX/DXYS10093common deletions respectively accounted for1case.3. The group of CNE abnormity compared with the group of SHOXabnormity in female, forearm length/height, forearm length/upper armlength,and leg length/height all had statistically significantdifferences(p<0.05),the first two diminished,the last raised up; Thediminished forearm length/upper arm length in the group of CNEabnormity compared with the other groups also had statistically significantdifferences(p<0.05); The diminished leg length/height in the group ofSHOX abnormity had statistically significant differences compared withother three groups, in addition to, compared with the group of normalcontrol, the diminished upper arm length/height and extremities-trunkratio,the increased leg circumference/height and BMI had statisticallysignificant differences(p<0.05).4. The group of CNE abnormity in male compared with the group ofSHOX abnormity and the group of non CNE/SHOX abnormity,all ofclinical phenotype indexes had no statistically significant differences(p>0.05). Compared with the group of normal control,sit height/height andforearm circumference/height increased,leg length/height and extremities-trunk ratio diminished had statistically significant differences(p<0.05); The group of SHOX abnormity compared with the other groups,forearm circumference/height increased,leg length/height diminished hadstatistically significant differences(p<0.05).5. The X-ray bone characteristic indexes in the prepuberty female,onlyincluded angle of distal ulna and radius had statistically striking differencesduring the four groups(p<0.01); In the prepuberty male, the included angleof distal ulna and radius had no statistically significant differences duringthe group of CNE deformity and the group of SHOXdeformity(P>0.05),but it had statistically striking differences comparedwith the normal control group(P<0.01).6. The X-ray bone characteristic indexes in all the purberty patients withISS had no statistically significant differences during the group of CNEdeformity and the group of SHOX deformity(P>0.05); Compared with thegroup of normal control, differences in height between the distal ulna andradius increased, angle of inclination of ulna and included angle of distalulna and radius diminished had statistically significant differences infemale (P<0.05); and only included angle of distal ulna and radius hadstatistically significant differences in male(P<0.05).Conclusion：1. In the501cases of ISS patients,abnormalities of SHOX patientsaccounted for22cases (4.39%), abnormalities of CNE patients accounted for36cases (7.19%); average height SD of the SHOX gene abnormalitygroup was (-2.950±1.474), average height SD of the CNE geneabnormality group was (-2.969±0.998), it had no significant differencebetween this two groups, suggested the same height difference resultfrom CNE abnormalities and the SHOX gene abnormalities.2. The decreasing trend in Forearm length/height and forearm length/arm length is more obvious when CNE abnormalities compared to theSHOX gene abnormalities in female, speculated that the CNEabnormalities may be more effected on forearm; When the SHOX gene wasabnormal, leg length/height diminished and calf circumference/heightincreased was significant, speculated that SHOX gene abnormalities impactleg development apparently.3.The clinical manifestation was similar between CNE abnormalitiescompared and the SHOX gene abnormalities in male, but they comparedwith the normal control, the clinical manifestation included orearm musclehypertrophy, short stature, short limbs and high trunk.4. The X-ray bone characteristic indexes in all the prepuberty patients，only included angle of distal ulna and radius can reflect the ulnaris of radialepiphysis fused in advanced. The CNE abnormalities leaded to itdiminished,and was significant in female.5. In all the puberty patients, the CNE abnormalities and the SHOXabnormalities can lead to the advanced fused in the ulnaris of radial epiphysis, but the indexes were different. In female, height between thedistal ulna and radius increased, angle of inclination of ulna and includedangle of distal ulna and radius diminished. In male, only included angle ofdistal ulna and radius diminished.6. The CNE abnormalities and the SHOX abnormalities can lead toabnormal clinical manifestation, but the indexes and the level of effect wasdifferent. According to the analysis of the subject,it was beneficial forscreening the CNE abnormalities patient and the SHOX abnormalitiespatient.