ABSTRACT
Objective@#To investigate the long-term effects of GnRHa treatment on final height gain, gonadal function, and body mass index(BMI) in children with central precocious puberty(CPP) or early and fast puberty(EFP), and to explore the influencing factors of height gain and early predictors.@*Methods@#Fifty patients with CPP and 44 patients with EFP who were treated with GnRHa for more than 2 years were enrolled(80 females and 14 males). Body height, bone age, BMI, gonads hormone, uterus and ovarian volumes(female), testicular volume(male), and other parameters before and after treatment were measured.@*Results@#(1)For girls: GnRHa plus GH treatment gained more final height compared with GnRHa treatment [(10.69±5.73) cm vs (7.42±5.76) cm, P<0.05]. Height lost >5cm at the initial treatment benefited much more for the final height compared with height lost<5cm [(10.65±3.32) cm vs (6.51±3.40) cm, P<0.01]. The proportion of overweight/obesity decreased when reaching the final height compared with the initial treatment and stopping the treatment. Serum LH level, uterine and ovarian volume were significantly decreased after stopping treatment compared with before treatment, and increased half a year to 1 year after stopping treatment.100% of girls had menarche and 95% reached the regular cycle 3 years after stopping treatment.(2)For boys: GnRHa plus GH treatment and GnRHa treatment gained height by(8.78±5.2) and(7.99±4.82) cm, respectively. Serum LH level and testicular volume were significantly decreased after stopping treatment as compared with those before treatment, and increased for half a year to 1 year after stopping treatment.@*Conclusion@#GnRHa treatment can significantly improve the final height for girls with CPP and EFP. The patients with more height lost could gain more height, which can be used as a predictor of height gain.
ABSTRACT
Objective:To investigate the long-term effects of GnRHa treatment on final height gain, gonadal function, and body mass index(BMI) in children with central precocious puberty(CPP) or early and fast puberty(EFP), and to explore the influencing factors of height gain and early predictors.Methods:Fifty patients with CPP and 44 patients with EFP who were treated with GnRHa for more than 2 years were enrolled(80 females and 14 males). Body height, bone age, BMI, gonads hormone, uterus and ovarian volumes(female), testicular volume(male), and other parameters before and after treatment were measured.Results:(1)For girls: GnRHa plus GH treatment gained more final height compared with GnRHa treatment [(10.69±5.73) cm vs (7.42±5.76) cm, P<0.05]. Height lost >5cm at the initial treatment benefited much more for the final height compared with height lost<5cm [(10.65±3.32) cm vs (6.51±3.40) cm, P<0.01]. The proportion of overweight/obesity decreased when reaching the final height compared with the initial treatment and stopping the treatment. Serum LH level, uterine and ovarian volume were significantly decreased after stopping treatment compared with before treatment, and increased half a year to 1 year after stopping treatment.100% of girls had menarche and 95% reached the regular cycle 3 years after stopping treatment.(2)For boys: GnRHa plus GH treatment and GnRHa treatment gained height by(8.78±5.2) and(7.99±4.82) cm, respectively. Serum LH level and testicular volume were significantly decreased after stopping treatment as compared with those before treatment, and increased for half a year to 1 year after stopping treatment. Conclusion:GnRHa treatment can significantly improve the final height for girls with CPP and EFP. The patients with more height lost could gain more height, which can be used as a predictor of height gain.
ABSTRACT
Objective To explore the etiology and clinical characteristics of short stature. Method Clinical data of 2075 children with short stature treated from May 1995 to July 2017 were retrospectively analyzed. The etiology and morbidity of pathological short stature and normal variant short stature were analyzed. The clinical characteristics of growth hormone deficiency (GHD) , idiopathic short stature (ISS) , constitutional delay in growth (CDG) and familial short stature (FSS) were analyzed. The etiological differences between severe short stature [height standard deviation score (SDS) ≤-3] and general short stature (height SDS＞-3) were analyzed. Results Among 2075 children diagnosed with short stature, 1719 (82.84％) were pathological short stature, among which GHD (38.60％) and ISS (22.02％) were more common. Normal variant short stature was found in 356 children (17.16％) , with FSS and CDG accounting for 10.70％ and 6.46％ respectively. There were statistically significant differences in the sex ratio, age at initial diagnosis, height SDS, body mass index (BMI) , bone age and bone age delay among children with four common childhood short stature (GHD, ISS, CDG and FSS) (all P＜0.01) . Boys were more than girls in four kinds of childhood short stature. The height SDS was the lowest in GHD group and the highest in CDG group; BMI was highest in GHD group, but lower in CDG and ISS group. Bone age delay was highest in GHD group and lowest in CDG group. In severe short stature group, the rates of complete GHD, multiple pituitary hormone deficiency, small for gestational age infant, Turner syndrome, hypothyroidism and Russell-Silver syndrome were higher than those in general short stature group, but the rates of partial GHD, ISS, FSS and CDG was lower than those in general short stature group. Conclusion The etiology of short stature is complex. Analysis of the etiology and clinical features is helpful for clinical diagnosis and treatment.
ABSTRACT
PTPN11 is the most common mutation gene of RAS disease, which is located in the upstream of RAS/MAPK pathway and participates in signal transduction. Because the molecular mechanism of RAS's disease involves the same pathway, it may present a certain commonality in clinic, but the different genotypes with PTPN11 mutation may also express different phenotypes. Therefore, it is not easy to identify and diagnose this disease early in clinic. The present article aims to analyze the correlation between the clinical phenotype and genotype of 4 patients with RAS disease.
ABSTRACT
The clinical features and laboratory data of two patients with congenital lipoid adrenal hyperplasia (CLAH)were collected. The genomic DNA was extracted from the peripheral blood white cells in the two patients and their family members and the STAR gene was screened for mutations by PCR and Sanger sequencing. Patient 1 was a girl aged 2 years and 8 months,and she visited us because of continual cyanosis for more than two years. Physical examination showed no obvious pigmentation or clitoral hypertrophy,and Tanner stage was B1P1. Clinical examination revealed serum ACTH 1 284.1 pg/ml and 17α-hydoxyprogesterone(17-OHP)0.54 ng/ml, with Karyotype 46, XX. Genetic analysis showed compound heterozygous mutations of c.201_202delCT and c.229C>T in the STAR gene. Her father carried heterozygous c.201_202delCT mutation, and her mother showed heterozygous c.229C>T mutation. Patient 2 was a girl aged 22 years and referred to us because of dark skin for more than 21 years. Physical examination revealed generalized hyperpigmentation,with Tanner stage B5P2. Hormone examination showed ACTH>2 000 pg/ml and serum cortisol 0.77μg/dl. Karyotype analysis revealed 46,XX. Genetic analysis found compound heterozygous mutations of c.64+1G>C and c.707_708delinsCTT in the STAR gene,which descended from her father and mother respectively. Of note,c.64+1G>C is a novel splicing mutation of STAR gene.
ABSTRACT
Objective To investigate the clinical characteristics and molecular pathological mechanism of McCune-Albright syndrome ( MAS) in order to provide a guidance for the precision medicine of MAS. Method The clinical data and genetic findings of 41 patients with MAS were analyzed retrospectively. Results (1) MAS girls had the phenotype of peripheral precocious puberty with premature sexual development and high estradiol, low LH and FSH, and the increased volume of uterus and ovary. ( 2 ) In 41 MAS cases, there were 17 cases with GNAS1 gene mutation, and the total positive rate was 41. 5%, of which the classic triad was 66. 7%, two signs 56. 3%, and 12. 5% in only one classic sign. GNAS1 gene mutation was found in 78. 6% of patients with polyostotic fibrous dysplasia of bone, while only 55. 0% in patients with cafe au lait skin spots. Children with precocious puberty and fibrous dysplasia of bone is an important basis for clinical diagnosis of MAS, but cafe au lait skin spots does not seem to be the specifical manifestation of MAS. Conclusion Clinically MAS was lack of typical clinical manifestations, and the most important clinical weight factor for the diagnosis of MAS was peripheral precocious puberty with fibrous dysplasia of bone. GNAS1 gene screening may be helpful to improve the clinical accurate diagnosis of MAS.
ABSTRACT
Objective To analyze the clinical characteristics of two patients with 3β-hydroxysteroid dehydrogenase deficiency and to explore their molecular genetic defects.Methods The clinical features and laboratory data of two patients were collected.The exons of HSD3B2 gene were amplified by PCR and sequenced by Sanger sequencing.Results Patient 1, aged 5 yrs old, was raised as a girl with 46, XY karyotype, presented with hyperpigmentation, female infant vulva, clitoral hypertrophy, and bilateral cryptorchidism;Patient 2, aged 11 yrs old, was raised as a girl at birth but as a boy after 1 yr old for known 46, XY karyotype, presented with hyperpigmentation, micropenis and severe hypospadias.Both patients had markedly elevated adrenocorticotropin and decreased cortisol.Two homozygous missense mutations in HSD3B2 gene were identified:conversions of codon Pro155 toLeu(p.P155L)inpatient1,andcodonAla82toThr(p.A82T)inpatient2,bothofwhichwerereportedforthe first time in China.Conclusion The patients with 3β-hydroxysteroid dehydrogenase deficiency in 46,XY karyotype mainly present with male pseudohermaphroditism and adrenocortical deficiency, and the diagnosis should rely on the steroids detection and HSD3B2 gene screening.
ABSTRACT
Objective To explore the causes of ambiguous genitalia.Methods Clinical data of 106 cases with ambiguous genitalia from Ruijin Hospital of Shanghai Jiaotong University School of Medicine were retrospectively analyzed.DNA fragments of related genes from parts of patients were amplified by means of polymerase chain reaction (PCR) and were directly sequenced to detect gene mutations.Results (1)The 106 ambiguous genitalia patients presented a variety of clinical phenotypes.Karyotype of 42 cases(39.6％)were 46,XX,while 62 cases(58.5％)were 46,XY and 2 cases(1.9％)were abnormal.(2)Forty(95.2％)patients with 46,XX were diagnosed with congenital adrenal hyperplasia(CAH) ;one case(2.4％) was adrenal cortical tumor and one case (2.4％) was 46,XX [sex determining region of Y choromosome (SRY) positive] male syndrome.(3) Fifty-three cases (85.5 ％) out of 46,XY karyotype were directly sequenced with steroid-5-alpha-reductase,alpha polypeptide 2 gene (SRD5A2),androgen receptor gene (AR) and steroidogenic factor-1 gene(SF-1).Sequencing analysis of SRD5A2 revealed 8 patients with compound heterozygous or homozygous mutations.A patient carried a novel missense mutation of SF-1 and another patient had a mutation of AR.(4) One abnormal karyotype was 46,XX/46,XY and the other was 46,XX/46,XY/46,X.+ may.ish (DYZ3 +) (DXZ1-).Conclusions (1) CAH is the most common cause of genital ambiguity in 46,XX patients but some rare causes such as adrenal cortical tumors or SRY positive should not be ignored.(2) To find the causes of 46,XY genital ambiguity,direct DNA sequencing analysis of candidate genes would be the better choice because of the complicate pathogenesis.(3)Abnormal karyotype also can lead to ambiguous genitalia.
ABSTRACT
Objective To explore the value of amino-terminal propeptide of C-type natriuretic peptide (NTproCNP) in evaluating the efficacy of therapy with recombinant human growth hormone ( rhGH ) in patients with idiopathic short stature (ISS) and isolated growth hormone deficiency ( IGHD ).Methods Forty-eight prepubertal children( IGHD n=25,ISS n=23 ) treated for at least 1 year with rhGH were included.Serum insulin-like growth factor- Ⅰ ( IGF- Ⅰ ) and NTproCNP levels were measured before starting treatment and 6 months later.Twelve months after starting treatment,all patients were assessed and annual growth velocity ( GV ),height standard deviation score ( HTSDS),and gained HTSDS (△HTSDS) were recorded.Results In GHD group,positive relationships between GV and change of IGF- ISDS( △IGF- ISDS ),GV and change of NTproCNP concentrations(△NTproCNP) were found( r=0.407,P=0.044 ;r=0.490,P=0.013 ).GH peak value was also positively associated with IGF- ISDS and NTproCNP before therapy ( r =0.558,P =0.004; r =0.630,P =0.001 ).△IGF- ISDS and △NTproCNP were positively associated after therapy ( r =0.466,P =0.019 ).In ISS group,GV was associated with △NTproCNP ( r=0.845,P＜ 0.01 ).Conclusions NTproCNP is a novel biomarker of growth as its level increases during growth-promoting treatment.Furthermore,IGF- Ⅰ is also valuable in evaluating the efficacy of rhGH therapy in short stature patients.
ABSTRACT
Objective To observe the final adult height (FAH) outcome and influencing factors in Turner′s Syndrome(TS) children treated with recombinant human growth hormone ( rhGH ).Methods Thirty TS children treated with rhGH were compared with 16 TS children without rhGH treatment and were followed up to achieve their FAH.Comparisons were made regarding predicted adult height (PAH),height standard deviation score for chronological age( HtSDScA ),height SDS for BA( HtSDSRA ),and growth velocity ( GV ) between rhGH treatment and without treatment groups and between the onset and by the end of rhGH treatment group.The factors determining FAH were also evaluated.Results FAH in rhGH treatment group was obviously improved as compared with untreatment group[ ( 149.5±6.3 vs 142.4±5.2) cm,P＜0.01 ].FAH in treatment group was positively correlated with height standard deviation score for chronological age ( Ht0 SDSCA ),Hto SDS for BA ( Hto SDSBA ),height age ( HA0 ) at preliminary diagnosis,and correlated with duration of rhGH therapy,duration of estrogen-free rhGH therapy,and PAH0SDS at preliminary diagnosis.Stepwise regression analysis indicated that duration of estrogen-free rhGH therapy and PAH0 SDS were the variables with the greatest identified influence on FAH (F =11.56 and F =86.91,P＜ 0.01 ).FAH in the 45,XO group was significantly different from the mosaicism group (45,XO/46,XX ) [ ( 147.2 ± 6.3 vs 153.3±6.4) cm,P =0.038].Conclusion rhGH treatment is efficacious in improving FAH of TS children,but a variability in the magnitude of the response to rhGH is recognized.Duration of estrogen-free rhGH therapy and PAH0SDS are the variables with the greatest identified influence on FAH,and karyotype may be one of the influence factors.rhGH treatment should be initiated as early as possible and sufficient course of estrogen-free rhGH therapy is needed to yield a satisfactory FAH.
ABSTRACT
Objective To assess the efficacy of gonadotropin-releasing hormone analogue(GnRHa)with or without recombinant human growth hormone(rhGH)treatment in Chinese short pubertal children with non-growth hormone deficiency.Methods Of 42 short pubertal children(14 males,28 females)without growth hormone deftcieney,the average age was(11.6±0.8)year.30 children were treated with slow release GnRHa with initial dose (100μg·kg-1·d-1,28d)and maintenance dose(60-80μg·kg-1·d-1,28d)labd rgGH with initial dose(0.15IU·kg-1·d-1)and maintenance dose(0.10-0.15IU·kg-1·d-1)for at least 1year.16 of them were still ongoing till the end of the second year.12 children were treated with GnRHa alone by initial dose(100μg·kg-1·d-1,28d)and maintenance dose (60-80μg·kg-1·d-1,28d),and 7 of them remained on it for 2 years.Dynamic changes including annual growth velocity(GV),bone age(BA)/chronologic age(CA)ratio,Tanner stage,height SDS for CA (HtSDSCA),height SDS for BA(HtSDSBA),and predicted adult height (PAHSDS)were observed.Results By the end of the first year tretment with combination therapy,the following parameters:GV,HtSDSCA,HtSDSBA,and PAHSDS all increased significantly(all P<0.05).Treatment with GnRHa alone did not yield significant changes in GV,HtSDSCA,HtSDSBA,and PAHSDS(all P>0.05).Changes in GV,HtSDSBA,and PAHSDS between these two groups were statistically significant(all P<0.05).By the end of the second year treatment,in the combination group,GV slowed from 6.7 to 5.5 cm/year(P<0.05).HtSDSCA,HtSDSBA,PAHSDS increased(all P<0.05).In the group with GnRHa treatment alone,GV slowed from 4.0 to 3.6 cm/year(P>0.05).HtSDSCA,HtSDSBA,PAHSDS increased(all P>0.05).Changes in GV,HtSDSCA,HtSDSBA,and PAHSDS between these 2 groups were statistically significant respectively(all P<0.05).Conclusion This combined treatment regimen significantly impreved the growth by increasing growth rate and delaying bone matumtion in pubertal chidren without growth hormone deficiency.Further study is needed to verify beneficial effects on the final height gain.
ABSTRACT
Objectives To evaluate final adult height(FAH), lipid profile, sexual development, and quality of life in individuals with childhood-onset growth hormone deficiency (CO-GHD) during the transition from childhood to adulthood, to reassess the function of GH-IGF-I axis, and to explore effective managements for different types of GHD in each period. Methods Totally 80 CO-GHD patients were divided into 2 groups; 22 patients with isolated growth hormone deficiency ( IGHD) and 58 patients with multiple pituitary hormone deficiencies (MPHD); 62 male (age ≥18 years) and 18 female ( age ≥ 16 years) patients. The clinical and biochemical parameters, education and occupation, rhGH, and other hormones therapy in the past were followed up. Results rhGH replacement improved FAH of patients with GHD. The incidences of either hyperlipidemia (39.0% , 47.4%) or fatty liver disease (26.8%, 31.6%) showed no statistically significant changes between 2 groups with and without rhGH replacement. Mean value of IGF-I SDS was significantly higher in IGHD group than that in MPHD group (-1.43±0. 31,-3. 01 ±0. 66) ,and also IGFBP3(-2. 10±0. 33,-3. 17±0. 19,all P< 0.05 ). Patients with IGHD had normal sexual development, but the incidence of sexual dysfunction accounted for 79.7% in MPHD group. Conclusions rhGH improves FAH of individuals with CO-GHD. Patients with CO-GHD should be followed during the transition period; GHD patients carry a high risk of metabolic abnormalities in the adulthood; IGHD female can give birth to offsprings; patients with MPHD have gonadotrophin deficiency of varying degrees.
ABSTRACT
Objective To investigate the effect of short stature homeobox (SHOX) gene promoter-372G →A mutation on the promoter activity and its mechanism.Methods The luciferase report gene vectors containing human SHOX gene promoter-372G or -372A were contructed.Their transcription activities were detected in chicken chondrocytes.Double-stranded DNA probes containing-372G or-372A were produced by PCR,and used for detecting the affinity with nuclear transcription factors by electrophoretic mobility shift assay(EMSA).Results The transcription activity in a-372A promoter construct was significantly higher than that in the wild type-372G (P<0.01).The result of EMSA showed that-372A gene mutation resulted in loss of the binding affinity to nuclear transcription factors.Conclusion The-372A mutation increases SHOX promoter activity with decreased DNA binding affinity to transcription factors,which may contribute to impaired long bone growth in patients with idio pathic short stature.
ABSTRACT
Objective To investigate the effects of diets with different calorie and nutritional values on pubertal onset in female rats. Method Female Wistar rat models receiving calorie-deprived (group R) (Experiment 1) ,fat-rich(group F) ,glucose-rich(group G) and protein-rich(group P) (Experiment 2) test diets were established,and rats receiving diets with normal caloric value were considered as control group (group C). The body weight (BW) ,food-intake and vaginal patency (VP) were observed. The rats were killed at the day of vaginal patency. The BW, uterus weight (UW), uterus index (UI), calorie intake per day (CI), perirenal fat weight (PFW) and perirenal fat index (PFI) were measured. The serum levels of leptin, ghrelin, IGF- Ⅰ were tested by means of ELISA.Results Experiment 1:The VP was retarded in group R compared with group C (P<0. 01). There was a significant difference in BW, UW,UI ,CI,leptin and ghrelin at the VP day between group R and group C (all P<0.01) ,and no significant difference in IGF- Ⅰ levels between these two groups. Experiment 2 :The VP was retarded in group F,group G and group P in comparison with group C (P<0.01). The BW, PFW and PFI in group G and group F were markedly higher than those in group P and group C. The leptin level in group F was the highest, and the lowest in group P. The ghrelin level in group G was the highest,and that in group P was the lowest. However,there were no significant differences in IGF- Ⅰ and UI among these, four groups. Conclusion The normal pubertal onset of female rats requires sufficient caloric stores and balanced nutrient. Diets malnutrition and fat-rich, glucoserich and protein-rich test diets all delay pubertal onset in female rats.
ABSTRACT
<p><b>OBJECTIVE</b>[corrected] To investigate the mutation at the transmembrane domain of fibroblast growth factor receptor 3 (FGFR3) nucleotide 1138 site for identifying the major pathologic mechanism of achondroplasia (ACH) and to evaluate the efficacy of denaturing gradient gel electrophoresis(DGGE) method for screening the point mutations.</p><p><b>METHODS</b>The genomic DNA from 17 clinically diagnosed ACH patients where analysed by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) with Sfc I and Msp I restriction endonucleases and by PCR-DGGE technique for screening.</p><p><b>RESULTS</b>G to A transition mutation at nucleotide 1138 was detected in 14/17 of the ACH patients as heterozygotes by PCR-RFLP with Sfc I digestion. No 1138 G to C transition was detected by Msp I digestion. All of the 14 samples with G to A mutation were also found to be positive for point mutation by PCR-DGGE. No mutation was detected in 3 negative samples by PCR-RFLP, implying that there was actually no point mutation in this amplified region.</p><p><b>CONCLUSION</b>Nucleotide 1138 in transmembrane domain of FGFR3 gene is the hot point for mutation in ACH and hence its major pathologic cause. PCR-DGGE is a sensitive and reliable technique for point mutation screening, especially for the heterozygotes.</p>
Subject(s)
Female , Humans , Male , Achondroplasia , Genetics , DNA , Chemistry , Genetics , DNA Mutational Analysis , Point Mutation , Polymorphism, Restriction Fragment Length , Polymorphism, Single-Stranded Conformational , Protein-Tyrosine Kinases , Receptor, Fibroblast Growth Factor, Type 3 , Receptors, Fibroblast Growth Factor , GeneticsABSTRACT
0.05). (2)Carbohydrate, protein and fat intake in GDM group (as % kJ) was 51.9?7.2,17.5?0.9 and 30.6?1.3, respectively. Carbohydrate, protein and fat intake in NP group (as % kJ) was 53.6?8.1, 18.3?1.1 and 28.1?2.3 respectively. Fat intake (as % kJ) in GDM group was significantly higher than that in NP group (P0.05). (3) Polyunsaturated fatty acids(PUFA) in GDM group (as % kJ) (8.3?0.5) was lower than that in NP group (10.1?0.4)(P