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The growth plate (cartilage tissue) is the key to bone development and linear growth.However, as the adolescence proceeds, the proliferation capacity of the growth plate will be continuously consumed, and finally the growth plate will be closed.A variety of regulatory factors control chondrocyte proliferation and differentiation through different mechanisms.Endocrine regulators (including growth hormone, insulin-like growth factor, thyroxine, sex hormone, glucocorticoid, etc.) and transcription factors play an important role in regulating the development of growth plates through systematic modulation.In addition, such local regulatory factors as Indian hedgehog protein, parathyroid hormone-related peptide, bone morphogenetic protein and fibroblast growth factor also regulate the development of the growth plate.In this paper, the regulatory mechanism for chondrocyte proliferation and differentiation was summarized.
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OBJECTIVE@#To explore the genetic basis for a child with Rothmund-Thomson syndrome (RTS).@*METHODS@#The child has featured poikeloderma, short stature, cataract, sparse hair and skeletal malformation. Peripheral blood samples of the child and her family members were collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing.@*RESULTS@#The child was found to harbor compound heterozygous variants of the RECQL4 gene, namely c.1048_1049delAG and c.2886-1G>A, among which c.2886-1G>A was unreported previously. According to the ACMG guidelines, the c.1048_1049delAG was predicted to be pathogenic (PVS1+PM3_Strong+PM2), while the c.2886-1G>A was predicted to be likely pathogenic (PVS1+PM2).@*CONCLUSION@#The compound heterozygous variants of the RECQL4 gene probably underlay the pathogenesis of RTS in this patient. Above finding has enriched the mutational spectrum of the RECQL4 gene.
Subject(s)
Child , Female , Humans , Family , Mutation , RecQ Helicases/genetics , Rothmund-Thomson Syndrome/genetics , Exome SequencingABSTRACT
Congenital lipoid adrenal hyperplasia (CLAH) is a rare autosomal recessive disorder, which is characterized by adrenal insufficiency and 46, XY sex reversal. Two cases of CLAH with 46, XY karyotype exhibited male external genitalia were reported to explore the clinical and genetic features. A retrospective analysis of CLAH with relevant literatures was performed.
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To report the clinical, imaging, and pathological feature of a rare case of central precocious puberty with primary pigmented nodular adrenocortical disease(PPNAD), and to conduct a retrospective analysis of PPNAD with relevant literatures. The pubic hair was found in the child for more than one year. Physical examination showed Cushing′s syndrome. ACTH in blood decreased, cortisol rhythm was disordered, 24-hour urine free cortisol increased and the paradoxical increase of urine free cortisol after high dose dexamethasone suppression test. Adrenal enhancement computed tomography(CT)showed multiple small nodular shadows in bilateral adrenal glands. Gonadotropin releasing hormone(GnRH)stimulation test supported central precocious puberty and GnRH analogue was used to control the sexual development. PPNAD was supported by pathology result. The symptoms of Cushing′s syndrome were relieved partially after left adrenalectomy.
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To report the process of diagnosis and treatment of 1 case with SRY gene mutation of 46, XY complete gonadal dysplasia, and to discuss the clinical characteristics, diagnosis and treatment of the disease.Due to clitoral enlargement for 8 months, a 9 years old girl was admitted to the Children′s Hospital Affiliated to Zhejiang University School of Medicine.Previously, she had early breast development, and suffered from high gonadotropin expression when she was 6 years and 4 months old.Physical examination: breast B3 stage, female vulva, clitoris hypertrophy, normal urethra, normal vaginal opening, slightly thick hymen ring, the development of pubic hair was 2 stages, and Prader score level 1.Laboratory data showed elevated levels of estradiol, testosterone, and human chorionic gonadotrophin.Genetic examination revealed that the chromosome karyotype was 46, XY and SRY gene detection was positive.Therefore, the patient was diagnosed with 46, XY complete gonadal dysplasia.Bilateral gonadectomy was performed, and the posto-perative pathological diagnosis was bilateral gonadoblastoma with left dysgerminoma.The tumor did not recur after che-motherapy.The etiology of early breast development needs to be carefully identified.Patients with sexual characteristics dysplasia need to accept the chromosome karyotype analysis and gene detection, and surgical exploration should be performed when necessary for a correct diagnosis as soon as possible.
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Gonadotropin-releasing hormone (GnRH) dependent precocious puberty/central precocious puberty (GDPP/CPP) is one of the common diseases of the pediatric endocrine system.CPP is mainly treated with gonadotropin-releasing hormone analogues (GnRHa) internationally.They slow the progression of bone age and improve adult height in children with CPP by inhibiting the activity of the hypothalamic-pituitary-gonadal axis and the secretion of sex hormones.In clinical practice, the populations who benefit from GnRHa treatment and the best GnRHa treatment plan still need to be investigated, and the long-term efficacy and safety evidence of GnRHa should be further improved.
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Type 1 diabetes(T1D)is and organ-specific autoimmune disease resulting from immune-mediated loss of pancreatic beta cells leading to insulin deficiency and hypoglycemia.It is the most common form of diabetes in children, and its incidence is on the rise.The etiology of T1D is hypothesized to involve genetic and environmental factors that result in the T-cell mediated destruction of pancreatic beta cells.The process usually progresses over a period of many months to years, during which period patients are asymptomatic and euglycemic, but positive for relevant autoantibodies.Symptomatic hyperglycemia and frank diabetes occurs after a long latency period, which reflects the large percentage of beta cells that need to be destroyed before overt diabetes become evident.We here will present genetic, enterovirus and gut microbiome factors that affect the pathogenesis of type 1 diabetes, which may help detect possible prevention and treatment of type 1 diabetes in the future.
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OBJECTIVE@#To explore the genetic basis for a child with spondyloepimetaphyseal dysplasia type 1 and joint laxity.@*METHODS@#High-throughput sequencing and Sanger sequencing were used to analyze potential variant of the B3GALT6 gene.@*RESULTS@#DNA sequencing has identified 2 variants of the B3GALT6 gene in the patient, namely c.694C>T and c.539_540insCCT, which were respectively derived from his father and mother.@*CONCLUSION@#The c.694C>T and c.539_540insCCT variants of the B3GALT6 gene probably underlie the disease in the patient. The result has enabled molecular diagnosis, genetic counseling and prenatal diagnosis for his family.
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Clinical features of and genetic mutations in two cases of pseudohypoparathyroidism type Ⅰ a(PHP Ⅰ a) with early-onset skin nodules were analyzed.Both of the two patients were males,and their ages at onset were 2 and 3 months respectively.They both presented with early-onset skin nodules as the main clinical manifestation,and were clinically characterized by a round face,short neck and early obesity.Histopathological examination of skin lesions showed subcutaneous ectopic osteogenesis in both patients.The first patient had low blood calcium,high blood phosphorus,high parathyroid hormone (PTH),and gene sequencing showed a heterozygous mutation c.399delT causing a T base deletion at position 399 in exon 5 of the GNAS gene.The second patient had normal blood calcium and phosphorus levels as well as normal PTH levels at early stage,and gene sequencing showed a heterozygous mutation c.939delT causing a T base deletion at position 939 in exon 9 of the GNAS gene.The blood PTH level was found to increase in the second patient after 1-year follow-up.Both the patients were confirmedly diagnosed with PHP Ⅰa.After treatment with vitamin D3,no new skin nodules occurred,and the blood calcium and phosphorus levels returned to normal.
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Objective@#To explore the feasibility of gender assignment in 46,XY disorders of sex development (DSD) with severe undermasculinisation mainly based on molecular diagnosis.@*Methods@#A retrospective study of 45 patients of 46, XY DSD with severe undermasculinisation were admitted between November 2015 and October 2018 at Children′s Hospital, Zhejiang University School of Medicine. The initial social gender were all female, of whom the external genital manifestations were Prader 0 to 2; the degree of masculinity was scored using external masculinisation score (EMS); the position and development of the gonads were examined by ultrasound, cystoscopy and laparoscopy, also including assessing the development of the Wolffian tube and the Müllerian tube. The level and ratio of testosterone to dihydrotestosterone before and after hCG stimulation were evaluated for the function of Leydig cell and 5α-reductase-2. Gender role scales and sandbox games were used to assess gender role behavior. Genital sensitivity to androgen stimulation was assessed; A panel including 163 genes related to gender development were determined by second-generation sequencing in all 45 patients. Finally, a multidisciplinary team (MDT) makes a gender assignment after a comprehensive analysis mainly based on the molecular etiological diagnosis.@*Results@#Thirty-nine out of 45 patients (87%) had an identifiable genetic etiology, and the remaining 6 (13%) were negative for genetic testing. Forty-five patients had EMS less than or equal to 3 points. Sexual psychological assessment was performed in 39 patients, with male dominance in 24 (62%) and female dominance in 15 (38%). The gender assignment was 23 cases (51%) for male and 19 cases (42%) for female, and 3 cases (7%) were not completely determined.@*Conclusions@#Molecular diagnosis provides a strong basis for appropriate gender assignment of 46, XY DSD children with severe undermasculinisation. Based on molecular diagnosis, each DSD should be analyzed by professional MDT to analyze the clinical symptoms/signs, gonadal development, gonad tumor risk, external genital morphology, sexual psychological assessment, potential fertility opportunities, parental views, Social and cultural factors, etc. make appropriate gender assignment.
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Objective To explore the significance of the cut point of peak level of luteinizing hormone (LH) in gonadotropin-releasing hormone (GnRH) agonist test in the diagnosis of precocious puberty in obese girls.Methods According to the diagnostic criteria of children's central precocious puberty diagnosis consensus (2015),796 cases of precocious puberty (peak level of LH ≥3.3 IU/L) in Children's Hospital of Zhejiang University School of Medicine from January 2014 to December 2015 were divided into normal weight group (573 cases),overweight group (170 cases) and obesity group (53 cases).The 3 groups were compared in terms of basic level of LH,basic level of follicle stimulating hormone (FSH),peak level of LH and FSH,ratio of LH (peak)/FSH (peak),sex hormone binding protein (SHBG),and children with 3.3 IU/L ≤peak level of LH ＜5.0 IU/L were followed up.The accuracy of the diagnosis of central precocious puberty using peak level of LH was analyzed by using receiver operating characteristic (ROC) curve.Results The median of LH (peak) in the obese group was 6.92 IU/L,the median of SHBG was 46.52 nmol/L,the median of LH (peak) in normal weight group was 8.92 IU/L,and the median of SHBG was 87.28 nmol/L.There were significant differences between the 2 groups (P ＜ 0.05,0.001).A total of 89 cases in normal weight group and 65 cases of obesity/overweight group (3.3 IU/L ≤peak level of LH ＜5.0 IU/L) were followed up for 1 year,and 18 cases in normal weight group and 33 cases in obesity/overweight group developed to central precocious puberty,while the number of cases in the 2 groups was significantly different (P ＜0.001).The ROC curve analysis showed that the cut point of peak level of LH was 4.16 IU/L,the sensitivity was 0.606,the specificity was 0.656,and the Jordan index was the largest (0.344).Conclusions The peak level of LH in GnRH agonist test is important for the diagnosis of central precocious puberty in girls,but the effect of body mass index on its cut point needs to be considered.
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Objective To evaluate the value of serum uric acid(UA)levels with reference to the age,waist circumference,and body mass index(BMI)in predicting the metabolic syndrome(MS)in obese children.Methods A total of 300 obese children,including 180 boys and 120 girls,were enrolled in this study.The height,BMI,waist and hip circumference,blood pressure,serum glucose,insulin and lipid profile in all participants were measured.Oral glucose tolerance test and insulin releasing test were performed.The boys or girls were divided into 4 groups according to the 4 quantile of UA level,respectively.The clinical characteristics and correlation of UA with the clinical indexes and MS components were compared.The binary Logistic regression analysis was applied in the risk of MS and its components for the 4 groups of obese children.The area under the receiver operating characteristic curve(ROC curve)of UA level,age,waist circumference and BMI were used to predict the MS.Results UA level was increased with the increase of age,waist circumference and BMI,and the UA level was significantly correlated with triacylglycerol,postprandial 2 h glucose(2 h PG)(r=0.196,0.174 in boys;r=0.291,0.179 in girls).In boys,the adjusted odds ratio and 95％CI of the highest quartile of UA for triglyceridemia was 2.71(95％CI:0.77-9.58);which in girls,the adjusted odds ratio and 95％CI of the highest quartile of UA for hyperglycemia,hypertension were 8.45(95％CI:1.76-40.52)and 3.93(95％CI:0.66-23.33),respectively,with significant differences.In boys,the area under the ROC curve of UA level,age,waist circumference and BMI which predict the MS were 0.652 0.626,0.621,0.62,respectively,and the differences were significant(all P<0.05).Conclusions The UA level is significantly correlated with the composition of MS,UA detection combining with reference to the age,waist circumference,and BMI is helpful for the identification of high risk groups of metabolic syndrome.
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Thyroid nodules in children exhibit differences in pathophysiology,clinical manifestation,and long-term outcomes compared with those in adults.Besides,the treatment which may be recommended for adults may not be suitable for children who are at low risk for death but at higher risk for long-term harm from exceedingly aggressive therapy.The evaluation of thyroid nodules includes risk factors,thyroid-related hormone,thyroid ultrasound and fineneedle aspiration biopsy,and so on.Benign lesions should be observed mainly by follow-up,however,for malignant lesions,total thyroidectomy or near is recommended,surveillance and follow-up should be maintained after thyroidectomy.
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<p><b>OBJECTIVE</b>To investigate the clinical symptoms and potential mutations in the PLA2G6 gene for a child with infantile neuroaxonal dystrophy.</p><p><b>METHODS</b>Clinical data of the patient was collected. The coding regions of PLA2G6 gene was subjected to Sanger sequencing using blood DNA from the patient and her parents.</p><p><b>RESULTS</b>The patient has presented with psychomotor regression and hypotonia, followed by development of tetraparesis. A novel homozygous mutation G68A in the PLA2G6 gene was found by DNA sequencing, while her parents were both heterozygous carriers.</p><p><b>CONCLUSION</b>The psychomotor regression and tetraparesis of the patient was caused by infantile neuroaxonal dystrophy due to a novel homozygous mutation in the PLA2G6 gene, which was inherited from her parents.</p>
Subject(s)
Adult , Child, Preschool , Female , Humans , Male , Base Sequence , Brain , Diagnostic Imaging , DNA Mutational Analysis , Group VI Phospholipases A2 , Genetics , Homozygote , Magnetic Resonance Imaging , Molecular Sequence Data , Mutation , Neuroaxonal Dystrophies , Diagnostic Imaging , Genetics , RadiographyABSTRACT
Islet β cell secretion deficiency and( or) the decreased insulin sensitivity of target tissue are the important pathophysiological mechanisms of diabetes. So,detection and assessment of isletβcell function in the early stages,could be of great significance for disease severity evaluation,early intervention and prognosis of the disease. At present,the main methods of the testing and assessment ofβcell function includeβcell function evaluating indexes,pulsatile insulin secretion,insulin secretion by glucose or non-glucose secretagogues and func-tion testing by other secretions of isletβcells. Among of them,βcell functional assessment methods by detecting C-peptide( especially aspects such as 90 minutes of C-peptide testing in mixed-meal tolerance test,urinary C-pep-tide creatinine ratio) have experienced some progress in recent years.
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Objective To explore the relationship between obese children with benign acanthosis ni-gricans and insulin-resistant and type 2 diabetes mellitus. Methods Levels of glucose, insulin, and glucose/ insulin ratio were measured on fasting blood specimens, and anthropometric parameters including waist/hip ratio, fat mass, body fat percentage and body mass index were examined in 42 obese children with benign acanthosis nigricans, 60 cases of simple obesity and 20 healthy children controls. Glucose tolerance tests were performed in groups of obese children with benign acanthosis nigricans and simple obesity, respectively. Results Two of 42 obese children with benign acanthosis nigricans were diagnosed as type 2 diabetes mellitus. The rate of abnormal glucose tolerance and levels of blood sugar during 60 min and 120 min after glucose tolerance were significantly higher in acanthosis nigricans children than those in simple obesity (P
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<p><b>OBJECTIVE</b>To establish the specific 16S-23S rRNA gene spacer regions in different bacteria using polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), DNA cloning and sequences analysis.</p><p><b>METHODS</b>A pair of primers were selected from highly conserved sequences adjacent to the 16S-23S rRNA spacer region. Bacterial DNA from sixty-one strains of standard bacteria and corresponding clinical isolates representative of 20 genera and 26 species was amplified by PCR, and further analyzed by RFLP, DNA cloning and sequences analysis. Furthermore, all specimens were examined by bacterial culturing and PCR-RFLP analysis. The evaluation of these assays in practical clinic practice was also discussed.</p><p><b>RESULTS</b>Restriction enzyme analysis revealed one, two or three bands or more observed among the 26 different standard strains. The sensitivity of PCR reached 2.5 colony-forming unit (CFU), and there was no cross reaction with human genomic DNA, fungus or virus. Fourteen species could be distinguished immediately by PCR, while another 10 species were further identified by Hinf I or Alu I digestion. The only difference between K.pneumoniae and E. durans was located at the site of the 779th nucleotide according to the sequence analysis and only XmaIII digestion could distinguish one from another. Of 42 specimens from septicemic neonates, 15 were identified as positive by blood culture at a rate of 35.7%. However, 27 specimens identified as positive by PCR, with a rate of 64.2%, a method significantly more effective than blood culture (P < 0.01). Of 6 cerebrospinal fluid (CSF) specimens, one tested positive for S.epidermidis was also positive by PCR, two culture negative were positive by PCR and diagnosed as S.epidermidis according to the DNA pattern. One positive for C.neoformans was negative by PCR. The other two specimens were negative by both PCR and culture.</p><p><b>CONCLUSIONS</b>The method of detecting bacterial 16S-23S rRNA spacer regions using PCR-RFLP techniques was specific, sensitive, rapid and accurate in providing a new technique for detecting pathogens in clinical bacterial infections.</p>
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Humans , Bacteria , Genetics , DNA, Bacterial , Chemistry , DNA, Ribosomal , Chemistry , Genes, rRNA , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , RNA, Ribosomal, 16S , Genetics , RNA, Ribosomal, 23S , Genetics , Sensitivity and Specificity , Sequence Analysis, DNAABSTRACT
Objective To detect and differentiate six major human herpesviruses DNA by PCR, RFLP, DNA clone and sequence analysis. Methods Based on the sequence of well coonserved regions of the DNA polymerse gene in human herpesvimses, we synthesized two pairs of primers, including one pair designed to amplify herpes simplex virus type 1 and 2, Epstein Barr virus and cytomegalovirus, other pair of primer to varicella zoster virus and human herpesvirus 6 by PCR. Identification of the virus species was achieved through restriction enzyme digestion with BamHI and BstUI. Results The products of six human herpesviruses after PCR amplification were from 510bp to 592bp and allowed characterization of herpesvirus type with restriction endonulease analysis. The sensitivity could reach 0.1fg DNA and had no cross reaction to human genomic DNA, bacteria, fungas and virus. 89 cerebrospinal fluids(CSF) and 75 blood specimens were tested for the presence of hepersvirus DNA by this PCR assay, in which 13(14.6%) CSF and 26(34.7%) blood specimens were positive. Comparatively, 10(13.3%) were positive by ELISA for HSVⅠ/Ⅱ,EBV,CMV IgM in blood specimens and significantly lower than that of the PCR rate (P