| Objective:Turner syndrome(TS)is caused by the complete or partial deletion or structural abnormality of an X chromosome in all or part of the somatic cells.It is characterized by short stature,ovarian dysplasia and somatic abnormalities,accompanied by varying degrees of brain dysplasia and non-verbal cognitive impairment.The purposes of this study are as follows:1.To explore the height improvement of patients with Turner syndrome after treatment with recombinant human growth hormone.At the same time,to find the effects of different karyotypes,initial treatment time,treatment duration and different initial bone age on height improvement;to explore the effect of growth hormone therapy on bone age in patients with TS.2.To explore the differences in TCM(Traditional Chinese Medicine)constitution and neurocognitive function of TS patients with different karyotypes,and to explore the effects of different genes on the growth and development of Turner syndrome patients.Methods:This study is divided into two parts:1.In study one,the basic information of patients with Turner syndrome had been recorded,including name,age,chromosome karyotype,birthplace,height of parents,initial treatment time,initial dose of recombinant human growth hormone treatment,height and weight of patients,body mass index(Body Mass Index,BMI),bone age,the deadline of follow-up years,height and weight of patients at the end of follow-up.The karyotypes of patients were divided into groups,and the therapeutic effects of growth hormone therapy among different karyo-types were compared.The height improvement of TS patients with different initial treatment time and treatment duration,the difference between genetic target height and actual height of TS patients,and the effect of growth hormone treatment on bone age of TS patients were compared.2.23 patients with TS from the first study were included.The karyotypes were divided into 45,X group and non-45,X group.The patients' basic information,physical examination data,laboratory examination data and family history were recorded.TCM physique evaluation,intelligence assessment,multi-dimensional cognitive ability assessment,magnetic resonance image collection and whole exon sequencing were performed on the patients with TS.Compare the differences of TCM physique between the two groups of TS patients,compare the differences of IQ scores and cognitive evaluation scores between the two groups,as well as the differences of cerebral cortex thickness and the volume of gray matter and white matter between the two groups.The intelligence assessment and multi-dimensional cognitive ability of TS patients are compared with the normal model group at the same time.According to the results of whole exon sequencing,to explore the effect of corresponding gene mutations on neurocognitive function in patients with TS.Results:1.The mean initial treatment age of the 206 TS patients is 9.9±3.2 years,the bone age is 8.6±2.8 years,the initial height is 120.2±13.9 cm,mean treatment duration is 2.8 years.Until the cut-off time for follow-up,the mean age is 12.8±3.0,and the bone age and height are 11.4±2.3 years and 138.0±13.0 cm respectively.Thereinto,the annual growth rate of patients in 45,X group and none-45,X group were 6.9±3.0 cm/years and 7.5±2.3 cm/years.The average improvement of height was 7.9±3.7 cm in 0.5-1.3 years and 11.5±3.3 cm in 1.3-2.1 years after treatment,respectively.The average improvement in 2.1-3.7 years was 19.2v5.0 cm,and in 3.7 years,the average height improvement was 32.8±10.7 cm.Meanwhile,we found that growth hormone treatment did not lead to excessive increase of bone age in patients with TS.2.Among the 23 TS patients included,there was no statistical difference in TCM constitution between the 45,X group and the non-45,X group.In intelligence assessment and multi-dimensional cognitive function,there were significant differences in analogy score,matrix reasoning score,digit span,memorization score,number comparison,lattice comparison and simple subtraction between the TS group and the normal model group(P<0.05),but there was no significant difference in total IQ and multi-dimensional cognition between the 45,X group and the non-45,X group(P>0.05).In terms of cerebral cortex thickness,we found there was no significant difference between 45,X group and non-45,X group(P>0.05).About the volume of gray matter and white matter of brain structure,we found no difference in the volume of gray matter in these two groups(P>0.05).However,after further grouping,we found some of the gray matter volumes of the patients with circular X chromosome are smaller than that in 45,X patients,including parahippocampal gyrus,superior temporal lobe,superior temporal pole,occipital lobe,superior frontal gyrus,middle frontal gyrus,inferior frontal gyrus and superior temporal gyrus,and the differences were statistically significant(P<0.05).Simultaneously,we found that the volume of hippocampal gray matter,insular gray matter and temporal middle lobe gray matter in 45,X patients were smaller than that in mosaic patients(P<0.05).About the brain white matter,there was no significant difference among the groups.In terms of the relationship between gene and brain cognition,we found that the score of matrix reasoning in STS gene mutation group was lower than that in non-mutation group.the score of number comparison of NLGN4X gene mutation group was lower than that of non-mutation group,and the digit span of MAOA gene mutation group was lower than that of non-mutation group,the differences mentioned above were statistically significant.About the correlation of gene and brain structure volume,the thickness of precentral cortex in STS gene mutation group was smaller than that in non-mutation group,and the difference was statistically significant.However,there was no significant difference in the volume of gray matter and white matter between these two groups.There was no significant difference in cerebral cortex thickness between MAOA mutation group and non-mutation group,but there were significant differences between these two groups in precentral gyrus,postcentral gyrus,parahippocampal gyrus,hippocampus,cingulum,cerebellum,temporal lobe,frontal lobe,superior frontal gyrus,middle frontal gyrus,inferior frontal gyrus,superior temporal gyrus,inferior temporal gyrus and middle temporal gyrus gray matter volume,and these aspects in mutation group were all smaller than non-mutation group.Finally,the white matter volume in MAOA gene mutation group was smaller than that in non-mutation group,and the difference was statistically significant(P<0.05).Conclusion:1.The height of patients with Turner syndrome treated with recombinant human growth hormone was significantly improved,and the treatment of growth hormone did not lead to excessive increase of bone age in patients with TS.With regard to different karyotypes,we found that the annual growth rate of the 45,X group was lower than that of none-45,X group.2.Among the patients with Turner syndrome,there was no significant difference in TCM constitution between the 45,X group and the non-45,X group.On the premise of no statistical difference in the baseline evaluation,there was no significant difference in total IQ,multi-dimensional cognition and brain structure volume between the two groups,but the patients with circular X chromosome developed more abnormally in gray matter than those in the 45,X group.With regard to the study of genes,STS gene and MAOA gene may be candidate genes for neurocognitive phenotype in patients with TS. |
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