BACKGROUND Sotos syndrome is an autosomal dominant disorder,whereas attention-deficit/hyperactivity disorder(ADHD)is a neurodevelopmental condition.This report aimed to summarize the clinical and genetic features of a...BACKGROUND Sotos syndrome is an autosomal dominant disorder,whereas attention-deficit/hyperactivity disorder(ADHD)is a neurodevelopmental condition.This report aimed to summarize the clinical and genetic features of a pediatric case of Soros syndrome and ADHD in a child exhibiting precocious puberty.CASE SUMMARY The patient presented with accelerated growth and advanced skeletal maturation;however,she lacked any distinct facial characteristics related to specific genetic disorders.Genetic analyses revealed a paternally inherited heterozygous synonymous mutation[c.4605C>T(p.Arg1535Arg)].Functional analyses suggested that this mutation may disrupt splicing,and bioinformatics analyses predicted that this mutation was likely pathogenic.After an initial diagnosis of Sotos syndrome,the patient was diagnosed with ADHD during the follow-up period at the age of 8 years and 7 months.CONCLUSION The potential for comorbid ADHD in Sotos syndrome patients should be considered to avoid the risk of a missed diagnosis.展开更多
Caused by the mutation of methyl-CpG binding protein 2(MeCP2),Rett syndrome leads to a battery of severe neural dysfunctions including the regression of motor coordination and motor learning.Current understanding has ...Caused by the mutation of methyl-CpG binding protein 2(MeCP2),Rett syndrome leads to a battery of severe neural dysfunctions including the regression of motor coordination and motor learning.Current understanding has revealed the motor cortex as the critical region mediating voluntary movement.In this review article,we will summarize major findings from human patients and animal models regarding the cortical synaptic plasticity under the regulation of MeCP2.We will also discuss how mutation of MeCP2 leads to the disruption of cortical circuitry homeostasis to cause motor deficits.Lastly,potential values of physical exercise and neuromodulation approaches to recover neural plasticity and motor function will be evaluated.All of this evidence may help to accelerate timely diagnosis and effective interventions for Rett syndrome patients.展开更多
BACKGROUND Special AT-rich sequence binding protein 2(SATB2)-associated syndrome(SAS;OMIM 612313)is an autosomal dominant disorder.Alterations in the SATB2 gene have been identified as causative.CASE SUMMARY We report...BACKGROUND Special AT-rich sequence binding protein 2(SATB2)-associated syndrome(SAS;OMIM 612313)is an autosomal dominant disorder.Alterations in the SATB2 gene have been identified as causative.CASE SUMMARY We report a case of a 13-year-old Chinese boy with lifelong global developmental delay,speech and language delay,and intellectual disabilities.He had short stature and irregular dentition,but no other abnormal clinical findings.A de novo heterozygous nonsense point mutation was detected by genetic analysis in exon 6 of SATB2,c.687C>A(p.Y229X)(NCBI reference sequence:NM_001172509.2),and neither of his parents had the mutation.This mutation is the first reported and was evaluated as pathogenic according to the guidelines from the American College of Medical Genetics and Genomics.SAS was diagnosed,and special education performed.Our report of a SAS case in China caused by a SATB2 mutation expanded the genotype options for the disease.The heterogeneous manifestations can be induced by complicated pathogenic involvements and functions of SATB2 from reviewed literatures:(1)SATB2 haploinsufficiency;(2)the interference of truncated SATB2 protein to wild-type SATB2;and(3)different numerous genes regulated by SATB2 in brain and skeletal development in different developmental stages.CONCLUSION Global developmental delays are usually the initial presentations,and the diagnosis was challenging before other presentations occurred.Regular follow-up and genetic analysis can help to diagnose SAS early.Verification for genes affected by SATB2 mutations for heterogeneous manifestations may help to clarify the possible pathogenesis of SAS in the future.展开更多
Myelodysplastic syndromes have increased in frequency and incidence in the American population, but patient prognosis has not significantly improved over the last decade. Such improvements could be realized if biomark...Myelodysplastic syndromes have increased in frequency and incidence in the American population, but patient prognosis has not significantly improved over the last decade. Such improvements could be realized if biomarkers for accurate diagnosis and prognostic stratification were successfully identified. In this study, we propose a method that associates two state-of-the-art array technologies-single nucleotide polymorphism (SNP) array and gene expression array-with gene motifs considered transcription factor -binding sites (TFBS). We are particularly interested in SNP-containing motifs introduced by genetic variation and mutation as TFBS. The potential regulation of SNP-containing motifs affects only when certain mutations occur. These motifs can be identified from a group of co-expressed genes with copy number variation. Then, we used a sliding window to identify motif candidates near SNPs on gene sequences. The candidates were filtered by coarse thresholding and fine statistical testing. Using the regression-based LARS-EN algorithm and a level-wise sequence combination procedure, we identified 28 SNP-containing motifs as candidate TFBS. We confirmed 21 of the 28 motifs with ChIP-chip fragments in the TRANSFAC database. Another six motifs were validated by TRANSFAC via searching binding fragments on coregulated genes. The identified motifs and their location genes can be considered potential biomarkers for myelodysplastic syndromes. Thus, our proposed method, a novel strategy for associating two data categories, is capable of integrating information from different sources to identify reliable candidate regulatory SNP-containing motifs introduced by genetic variation and mutation.展开更多
Viral entry into the host is the earliest stage of infection in the viral life cycle in which attachment proteins play a key role. VP31(WSV340/WSSV396), an envelope protein of white spot syndrome virus(WSSV), contains...Viral entry into the host is the earliest stage of infection in the viral life cycle in which attachment proteins play a key role. VP31(WSV340/WSSV396), an envelope protein of white spot syndrome virus(WSSV), contains an Arg-Gly-Asp(RGD) peptide domain known as a cellular attachment site. At present, the process of VP31 interacting with shrimp host cells has not been explored. Therefore, the VP31 gene was cloned into p ET30a(+), expressed in Escherichia coli strain BL21 and purifi ed with immobilized metal ion affi nity chromatography. Four gill cellular proteins of shrimp( Fenneropenaeus c hinensis) were pulled down by an affi nity column coupled with recombinant VP31(r VP31), and the amino acid sequences were identifi ed with MALDI-TOF/TOF mass spectrometry. Hemocyanin, beta-actin, arginine kinase(AK), and an unknown protein were suggested as the putative VP31 receptor proteins. SDS-PAGE showed that AK is the predominant binding protein of VP31. An i n vitro binding activity experiment indicated that recombinant AK's(r AK) binding activity with r VP31 is comparable to that with the same amount of WSSV. These results suggested that AK, as a member of the phosphagen kinase family, plays a role in WSSV infection. This is the fi rst evidence showing that AK is a binding protein of VP31. Further studies on this topic will elucidate WSSV infection mechanism in the future.展开更多
The peritrophic membrane plays an important role in the defense system of the arthropod gut. The digestive tract is considered one of the major tissues targeted by white spot syndrome virus （WSSV） in shrimp. In this...The peritrophic membrane plays an important role in the defense system of the arthropod gut. The digestive tract is considered one of the major tissues targeted by white spot syndrome virus （WSSV） in shrimp. In this study, the nucleotide sequence encoding peritrophin-like protein of Litopenaeus vannamei （LvPT） was amplified from a yeast two-hybrid library of L. vannamei. The epitope peptide of LvPT was predicted with the GenScript OptimumAntigenTM design tool. An anti-LvPT polyclonal antibody was produced and shown to specifically bind a band at -27 kDa, identified as LvPT. The LvPT protein was expressed and its concentration determined. LvPT dsRNA （4 pg per shrimp） was used to inhibit LvPT expression in shrimp, and a WSSV challenge experiment was then performed with reverse gavage. The pleopods, stomachs, and guts were collected from the shrimp at 0, 24, 48, and 72 h post-infection （hpi）. Viral load quantification showed that the levels of WSSV were significantly lower in the pleopods, stomachs, and guts of shrimp after LvPT dsRNA interference than in those of the controls at 48 and 72 hpi. Our results imply that LvPT plays an important role during WSSV infection of the digestive tract.展开更多
Mutations in the WFS1 gene have been reported in Wolfram syndrome (WFS), a rare and autosomal recessive disorder defined <span style="font-family:Verdana;">by early onset of diabetes mellitus and progr...Mutations in the WFS1 gene have been reported in Wolfram syndrome (WFS), a rare and autosomal recessive disorder defined <span style="font-family:Verdana;">by early onset of diabetes mellitus and progressive optic and hearing impairment. Only few data are available concerning the association between clinical and molecular aspects of the WFS. We present a consanguineous family with a patient presenting an early onset of WFS and severe manifestations. Sequencing of </span><i><span style="font-family:Verdana;">WFS1</span></i><span style="font-family:Verdana;"> gene was performed for all the family members to search for responsible mutation and bioinformatics tools </span><span style="font-family:Verdana;">were </span><span style="font-family:;" "=""><span style="font-family:Verdana;">conducted to predict its effect on structure and function of the protein. We have detected a novel frameshift mutation in the proband at homozygous state and at the heterozygous state in the parents who have no WFS manifestations. In silico analysis predicted the pathogenicity of the mutation and could lead to a complete loss of its function. Thus, 3D modeling showed that the mutation abolishes the interaction of the CaM binding region to the N-terminal of WFS1 and then impairs the W</span><span style="font-family:Verdana;">FS1-CaM complex formation. Genotype-phenotype correlation study show</span><span style="font-family:Verdana;">s that the novel mutation predisposes to early onset of diabetes and severe symptoms observed in the proband. We also report the effect of the frameshift mutation on the CaM-WFS1 impaired binding, and we discuss its possible consequence in pancreatic </span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">-cells dysfunction and its role in the early onset of diabetes. In conclusion, the combination of impaired functions of WFS1 including unproper interaction of the CaM, Ca</span><sup><span style="font-family:Verdana;">2+</span></sup><span style="font-family:Verdana;"> uptake, mitochondrial dysfunction, and apoptosis under the ER stress could be involved in the severe phenotype and early onset of WFS of our patient.</span></span>展开更多
Objective To identify the changes in serum insulin like growth factor Ⅰ (IGF Ⅰ) and IGF binding proteins (IGFBPs) in children with nephrotic syndrome (NS) and the effect of glucocorticoid on serum IGF Ⅰ and IGF...Objective To identify the changes in serum insulin like growth factor Ⅰ (IGF Ⅰ) and IGF binding proteins (IGFBPs) in children with nephrotic syndrome (NS) and the effect of glucocorticoid on serum IGF Ⅰ and IGFBPs Methods We measured serum IGF Ⅰ and IGFBPs levels by radioimmune assay and immune radiomagnetic assay in 36 children with NS, consisting of an active stage group (ANS, n=12), a remission stage group (RE, n=12), an active stage group with glucocorticoid treatment (GNS, n=12), and a normal control group (NC, n=10) Results 1) Compared to NC, serum levels of IGF Ⅰ and IGFBP 3 were decreased ( P <0 01); serum levels of IGFBP 1 and IGFBP 2 were increased ( P <0 01) in the ANS group 2) Serum levels of IGF Ⅰ and IGFBP 3 were higher and IGFBP 1 and IGFBP 2 were lower in the RE Group than in theANS Group ( P <0 01) 3) Compared to the ANS group, serum levels of IGF Ⅰ and IGFBP 3 were increased ( P <0 01) and serum levels of IGFBP 1 and IGFBP 2 were decreased ( P <0 01) in the GNS group 4) A correlation was found between serum levels of IGFBP 3 and albumin in the active stage group ( r =0 76, P <0 01) There was also a correlation between serum levels of IGF Ⅰ and IGFBP 3 and an inverse correlation between the serum level of IGF Ⅰ and serum levels of IGFBP 1 and IGFBP 2 in the ANS group No other correlations were observed Conclusions The serum levels of IGF Ⅰ and IGFBPs are altered in children in the active stage of NS, but return to normal in the remission stage GC treatment may influence serum IGF Ⅰ and IGFBPs in children with NS Changes in IGF Ⅰ and IGFBPs levels may play a role in the growth retardation of NS children展开更多
This multi-center, cross-sectional study investigated the association between serum testosterone （T） levels, serum sex hormone-binding globulin （SHBG） levels, and the risk of metabolic syndrome （MS） in 3332 adul...This multi-center, cross-sectional study investigated the association between serum testosterone （T） levels, serum sex hormone-binding globulin （SHBG） levels, and the risk of metabolic syndrome （MS） in 3332 adult Chinese men. The prevalence of MS was 34.7%, and men with MS had lower serum levels of total T （TT） and SHBG than those without MS （P 〈 0.001）. There was no significant difference in serum free T （FT） levels between subjects with and without MS （P = 0.627）. In logistic regression analysis, the association between MS and serum SHBG levels persisted after adjusting for age, body mass index （BMI）, smoking and drinking status, and serum TT （odds ratio [OR] 0.962, 95% confidence interval [95% CI] 0.954-0.969, P 〈 0.01）. However, the association between serum TT level and the risk of MS was weak after adjusting for age, BMI, SHBG level, and smoking and drinking status （OR 0,981, 95% CI 0.960-1.007）. Our study reveals that both serum TT and SHBG levels, but not serum FT, are inversely associated with the prevalence of MS and that serum SHBG is an independent and dominant risk factor for MS.This multi-center, cross-sectional study investigated the association between serum testosterone （T） levels, serum sex hormone-binding globulin （SHBG） levels, and the risk of metabolic syndrome （MS） in 3332 adult Chinese men. The prevalence of MS was 34.7%, and men with MS had lower serum levels of total T （TT） and SHBG than those without MS （P 〈 0.001）. There was no significant difference in serum free T （FT） levels between subjects with and without MS （P = 0.627）. In logistic regression analysis, the association between MS and serum SHBG levels persisted after adjusting for age, body mass index （BMI）, smoking and drinking status, and serum TT （odds ratio [OR] 0.962, 95% confidence interval [95% CI] 0.954-0.969, P〈 0.01）. However, the association between serum TT level and the risk of MS was weak after adjusting for age, BMI, SHBG level, and smoking and drinking status （OR 0,981, 95% CI 0.960-1.007）. Our study reveals that both serum TT and SHBG levels, but not serum FT, are inversely associated with the prevalence of MS and that serum SHBG is an independent and dominant risk factor for MS.展开更多
Objective To identify significant factors related to the apolipoprotein B/apolipoprotein A1 （apoB/A1） ratio and investigate the association between the apoB/A1 ratio and metabolic syndrome （MS） in polycystic ovary...Objective To identify significant factors related to the apolipoprotein B/apolipoprotein A1 （apoB/A1） ratio and investigate the association between the apoB/A1 ratio and metabolic syndrome （MS） in polycystic ovary syndrome （PCOS） women. Methods Totally 307 subjects with PCOS were collected and recruited fulfilling the revised 2003 Rotterdam diagnostic criteria. MS was diagnosed by the National Cholesterol Education Program-Adult treatment Panel （NCEP-ATP） III criteria. Results The prevalence of MS in PCOS women was 31.6%, whose average age was 26.2 ___＋ 5.2 years. The apoB/A1 ratio was significantly correlated with age, body mass index （BM1）, waist circumference （WC）, hip circumference, waist-to-hip ratio, blood pressure, metabolic abnormalities, sex hormone binding globulin （SHBG）, and free androgen index. In addition, SHBG had a significant association with all five component risk of MS. The increasing apoB/A1 ratio was associated with the prevalence of MS and was one of the risk factors of MS. Conclusion SHBG was considered as an additional potential factor in predicting the metabolic abnormity in PCOS women. The apoB/A1 ratio is associated with SHBG and might be an indicator of MS in PCOS women.展开更多
Awide spectrum of Androgen insensitivity syndrome （AIS） occur due to mutations in the androgen receptor（AR）. The clinical presentation of AIS ranges from a typically male phenotype with decreased body hair and/ or...Awide spectrum of Androgen insensitivity syndrome （AIS） occur due to mutations in the androgen receptor（AR）. The clinical presentation of AIS ranges from a typically male phenotype with decreased body hair and/ or oligospermia to a typically female phenotype with primary amenorrhea and without pubic and axillary hair;展开更多
文摘BACKGROUND Sotos syndrome is an autosomal dominant disorder,whereas attention-deficit/hyperactivity disorder(ADHD)is a neurodevelopmental condition.This report aimed to summarize the clinical and genetic features of a pediatric case of Soros syndrome and ADHD in a child exhibiting precocious puberty.CASE SUMMARY The patient presented with accelerated growth and advanced skeletal maturation;however,she lacked any distinct facial characteristics related to specific genetic disorders.Genetic analyses revealed a paternally inherited heterozygous synonymous mutation[c.4605C>T(p.Arg1535Arg)].Functional analyses suggested that this mutation may disrupt splicing,and bioinformatics analyses predicted that this mutation was likely pathogenic.After an initial diagnosis of Sotos syndrome,the patient was diagnosed with ADHD during the follow-up period at the age of 8 years and 7 months.CONCLUSION The potential for comorbid ADHD in Sotos syndrome patients should be considered to avoid the risk of a missed diagnosis.
基金Supported by the National Natural Science Foundation of China,No.81771222the Guangdong Province Basic and Applied Basic Research Fund Project,No.2019A1515011316the Guangzhou Science and Technology Plan Project,No.202007030011.
文摘Caused by the mutation of methyl-CpG binding protein 2(MeCP2),Rett syndrome leads to a battery of severe neural dysfunctions including the regression of motor coordination and motor learning.Current understanding has revealed the motor cortex as the critical region mediating voluntary movement.In this review article,we will summarize major findings from human patients and animal models regarding the cortical synaptic plasticity under the regulation of MeCP2.We will also discuss how mutation of MeCP2 leads to the disruption of cortical circuitry homeostasis to cause motor deficits.Lastly,potential values of physical exercise and neuromodulation approaches to recover neural plasticity and motor function will be evaluated.All of this evidence may help to accelerate timely diagnosis and effective interventions for Rett syndrome patients.
文摘BACKGROUND Special AT-rich sequence binding protein 2(SATB2)-associated syndrome(SAS;OMIM 612313)is an autosomal dominant disorder.Alterations in the SATB2 gene have been identified as causative.CASE SUMMARY We report a case of a 13-year-old Chinese boy with lifelong global developmental delay,speech and language delay,and intellectual disabilities.He had short stature and irregular dentition,but no other abnormal clinical findings.A de novo heterozygous nonsense point mutation was detected by genetic analysis in exon 6 of SATB2,c.687C>A(p.Y229X)(NCBI reference sequence:NM_001172509.2),and neither of his parents had the mutation.This mutation is the first reported and was evaluated as pathogenic according to the guidelines from the American College of Medical Genetics and Genomics.SAS was diagnosed,and special education performed.Our report of a SAS case in China caused by a SATB2 mutation expanded the genotype options for the disease.The heterogeneous manifestations can be induced by complicated pathogenic involvements and functions of SATB2 from reviewed literatures:(1)SATB2 haploinsufficiency;(2)the interference of truncated SATB2 protein to wild-type SATB2;and(3)different numerous genes regulated by SATB2 in brain and skeletal development in different developmental stages.CONCLUSION Global developmental delays are usually the initial presentations,and the diagnosis was challenging before other presentations occurred.Regular follow-up and genetic analysis can help to diagnose SAS early.Verification for genes affected by SATB2 mutations for heterogeneous manifestations may help to clarify the possible pathogenesis of SAS in the future.
基金supported by grants from NIH(No.1R01LM010185,1U01CA166886,and 1U01HL111560)
文摘Myelodysplastic syndromes have increased in frequency and incidence in the American population, but patient prognosis has not significantly improved over the last decade. Such improvements could be realized if biomarkers for accurate diagnosis and prognostic stratification were successfully identified. In this study, we propose a method that associates two state-of-the-art array technologies-single nucleotide polymorphism (SNP) array and gene expression array-with gene motifs considered transcription factor -binding sites (TFBS). We are particularly interested in SNP-containing motifs introduced by genetic variation and mutation as TFBS. The potential regulation of SNP-containing motifs affects only when certain mutations occur. These motifs can be identified from a group of co-expressed genes with copy number variation. Then, we used a sliding window to identify motif candidates near SNPs on gene sequences. The candidates were filtered by coarse thresholding and fine statistical testing. Using the regression-based LARS-EN algorithm and a level-wise sequence combination procedure, we identified 28 SNP-containing motifs as candidate TFBS. We confirmed 21 of the 28 motifs with ChIP-chip fragments in the TRANSFAC database. Another six motifs were validated by TRANSFAC via searching binding fragments on coregulated genes. The identified motifs and their location genes can be considered potential biomarkers for myelodysplastic syndromes. Thus, our proposed method, a novel strategy for associating two data categories, is capable of integrating information from different sources to identify reliable candidate regulatory SNP-containing motifs introduced by genetic variation and mutation.
基金Supported by the National Science Foundation for Post-Doctoral Scientists of China(No.2013M541965)the International Postdoctoral Academic Exchange Program+2 种基金the Qingdao Postdoctoral Science Foundation Funded Projectthe Construction Program for“Taishan Scholarship”of Shandong Province of Chinathe Program for Chinese Outstanding Talents in Agricultural Scientific Research
文摘Viral entry into the host is the earliest stage of infection in the viral life cycle in which attachment proteins play a key role. VP31(WSV340/WSSV396), an envelope protein of white spot syndrome virus(WSSV), contains an Arg-Gly-Asp(RGD) peptide domain known as a cellular attachment site. At present, the process of VP31 interacting with shrimp host cells has not been explored. Therefore, the VP31 gene was cloned into p ET30a(+), expressed in Escherichia coli strain BL21 and purifi ed with immobilized metal ion affi nity chromatography. Four gill cellular proteins of shrimp( Fenneropenaeus c hinensis) were pulled down by an affi nity column coupled with recombinant VP31(r VP31), and the amino acid sequences were identifi ed with MALDI-TOF/TOF mass spectrometry. Hemocyanin, beta-actin, arginine kinase(AK), and an unknown protein were suggested as the putative VP31 receptor proteins. SDS-PAGE showed that AK is the predominant binding protein of VP31. An i n vitro binding activity experiment indicated that recombinant AK's(r AK) binding activity with r VP31 is comparable to that with the same amount of WSSV. These results suggested that AK, as a member of the phosphagen kinase family, plays a role in WSSV infection. This is the fi rst evidence showing that AK is a binding protein of VP31. Further studies on this topic will elucidate WSSV infection mechanism in the future.
基金Supported by the National Basic Research Program of China(973 Program)(No.2012CB114403)the China Agriculture Research System-47(CARS-47)
文摘The peritrophic membrane plays an important role in the defense system of the arthropod gut. The digestive tract is considered one of the major tissues targeted by white spot syndrome virus （WSSV） in shrimp. In this study, the nucleotide sequence encoding peritrophin-like protein of Litopenaeus vannamei （LvPT） was amplified from a yeast two-hybrid library of L. vannamei. The epitope peptide of LvPT was predicted with the GenScript OptimumAntigenTM design tool. An anti-LvPT polyclonal antibody was produced and shown to specifically bind a band at -27 kDa, identified as LvPT. The LvPT protein was expressed and its concentration determined. LvPT dsRNA （4 pg per shrimp） was used to inhibit LvPT expression in shrimp, and a WSSV challenge experiment was then performed with reverse gavage. The pleopods, stomachs, and guts were collected from the shrimp at 0, 24, 48, and 72 h post-infection （hpi）. Viral load quantification showed that the levels of WSSV were significantly lower in the pleopods, stomachs, and guts of shrimp after LvPT dsRNA interference than in those of the controls at 48 and 72 hpi. Our results imply that LvPT plays an important role during WSSV infection of the digestive tract.
文摘Mutations in the WFS1 gene have been reported in Wolfram syndrome (WFS), a rare and autosomal recessive disorder defined <span style="font-family:Verdana;">by early onset of diabetes mellitus and progressive optic and hearing impairment. Only few data are available concerning the association between clinical and molecular aspects of the WFS. We present a consanguineous family with a patient presenting an early onset of WFS and severe manifestations. Sequencing of </span><i><span style="font-family:Verdana;">WFS1</span></i><span style="font-family:Verdana;"> gene was performed for all the family members to search for responsible mutation and bioinformatics tools </span><span style="font-family:Verdana;">were </span><span style="font-family:;" "=""><span style="font-family:Verdana;">conducted to predict its effect on structure and function of the protein. We have detected a novel frameshift mutation in the proband at homozygous state and at the heterozygous state in the parents who have no WFS manifestations. In silico analysis predicted the pathogenicity of the mutation and could lead to a complete loss of its function. Thus, 3D modeling showed that the mutation abolishes the interaction of the CaM binding region to the N-terminal of WFS1 and then impairs the W</span><span style="font-family:Verdana;">FS1-CaM complex formation. Genotype-phenotype correlation study show</span><span style="font-family:Verdana;">s that the novel mutation predisposes to early onset of diabetes and severe symptoms observed in the proband. We also report the effect of the frameshift mutation on the CaM-WFS1 impaired binding, and we discuss its possible consequence in pancreatic </span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">-cells dysfunction and its role in the early onset of diabetes. In conclusion, the combination of impaired functions of WFS1 including unproper interaction of the CaM, Ca</span><sup><span style="font-family:Verdana;">2+</span></sup><span style="font-family:Verdana;"> uptake, mitochondrial dysfunction, and apoptosis under the ER stress could be involved in the severe phenotype and early onset of WFS of our patient.</span></span>
文摘Objective To identify the changes in serum insulin like growth factor Ⅰ (IGF Ⅰ) and IGF binding proteins (IGFBPs) in children with nephrotic syndrome (NS) and the effect of glucocorticoid on serum IGF Ⅰ and IGFBPs Methods We measured serum IGF Ⅰ and IGFBPs levels by radioimmune assay and immune radiomagnetic assay in 36 children with NS, consisting of an active stage group (ANS, n=12), a remission stage group (RE, n=12), an active stage group with glucocorticoid treatment (GNS, n=12), and a normal control group (NC, n=10) Results 1) Compared to NC, serum levels of IGF Ⅰ and IGFBP 3 were decreased ( P <0 01); serum levels of IGFBP 1 and IGFBP 2 were increased ( P <0 01) in the ANS group 2) Serum levels of IGF Ⅰ and IGFBP 3 were higher and IGFBP 1 and IGFBP 2 were lower in the RE Group than in theANS Group ( P <0 01) 3) Compared to the ANS group, serum levels of IGF Ⅰ and IGFBP 3 were increased ( P <0 01) and serum levels of IGFBP 1 and IGFBP 2 were decreased ( P <0 01) in the GNS group 4) A correlation was found between serum levels of IGFBP 3 and albumin in the active stage group ( r =0 76, P <0 01) There was also a correlation between serum levels of IGF Ⅰ and IGFBP 3 and an inverse correlation between the serum level of IGF Ⅰ and serum levels of IGFBP 1 and IGFBP 2 in the ANS group No other correlations were observed Conclusions The serum levels of IGF Ⅰ and IGFBPs are altered in children in the active stage of NS, but return to normal in the remission stage GC treatment may influence serum IGF Ⅰ and IGFBPs in children with NS Changes in IGF Ⅰ and IGFBPs levels may play a role in the growth retardation of NS children
文摘This multi-center, cross-sectional study investigated the association between serum testosterone （T） levels, serum sex hormone-binding globulin （SHBG） levels, and the risk of metabolic syndrome （MS） in 3332 adult Chinese men. The prevalence of MS was 34.7%, and men with MS had lower serum levels of total T （TT） and SHBG than those without MS （P 〈 0.001）. There was no significant difference in serum free T （FT） levels between subjects with and without MS （P = 0.627）. In logistic regression analysis, the association between MS and serum SHBG levels persisted after adjusting for age, body mass index （BMI）, smoking and drinking status, and serum TT （odds ratio [OR] 0.962, 95% confidence interval [95% CI] 0.954-0.969, P 〈 0.01）. However, the association between serum TT level and the risk of MS was weak after adjusting for age, BMI, SHBG level, and smoking and drinking status （OR 0,981, 95% CI 0.960-1.007）. Our study reveals that both serum TT and SHBG levels, but not serum FT, are inversely associated with the prevalence of MS and that serum SHBG is an independent and dominant risk factor for MS.This multi-center, cross-sectional study investigated the association between serum testosterone （T） levels, serum sex hormone-binding globulin （SHBG） levels, and the risk of metabolic syndrome （MS） in 3332 adult Chinese men. The prevalence of MS was 34.7%, and men with MS had lower serum levels of total T （TT） and SHBG than those without MS （P 〈 0.001）. There was no significant difference in serum free T （FT） levels between subjects with and without MS （P = 0.627）. In logistic regression analysis, the association between MS and serum SHBG levels persisted after adjusting for age, body mass index （BMI）, smoking and drinking status, and serum TT （odds ratio [OR] 0.962, 95% confidence interval [95% CI] 0.954-0.969, P〈 0.01）. However, the association between serum TT level and the risk of MS was weak after adjusting for age, BMI, SHBG level, and smoking and drinking status （OR 0,981, 95% CI 0.960-1.007）. Our study reveals that both serum TT and SHBG levels, but not serum FT, are inversely associated with the prevalence of MS and that serum SHBG is an independent and dominant risk factor for MS.
基金the traditional Chinese medicine(TCM)clinical research base contribution subject of the State Administration of TCM of China(JDZX2012039)special scientific research of Chinese Medicine Industry of the State Administration of TCM of China(201207001)
文摘Objective To identify significant factors related to the apolipoprotein B/apolipoprotein A1 （apoB/A1） ratio and investigate the association between the apoB/A1 ratio and metabolic syndrome （MS） in polycystic ovary syndrome （PCOS） women. Methods Totally 307 subjects with PCOS were collected and recruited fulfilling the revised 2003 Rotterdam diagnostic criteria. MS was diagnosed by the National Cholesterol Education Program-Adult treatment Panel （NCEP-ATP） III criteria. Results The prevalence of MS in PCOS women was 31.6%, whose average age was 26.2 ___＋ 5.2 years. The apoB/A1 ratio was significantly correlated with age, body mass index （BM1）, waist circumference （WC）, hip circumference, waist-to-hip ratio, blood pressure, metabolic abnormalities, sex hormone binding globulin （SHBG）, and free androgen index. In addition, SHBG had a significant association with all five component risk of MS. The increasing apoB/A1 ratio was associated with the prevalence of MS and was one of the risk factors of MS. Conclusion SHBG was considered as an additional potential factor in predicting the metabolic abnormity in PCOS women. The apoB/A1 ratio is associated with SHBG and might be an indicator of MS in PCOS women.
文摘Awide spectrum of Androgen insensitivity syndrome （AIS） occur due to mutations in the androgen receptor（AR）. The clinical presentation of AIS ranges from a typically male phenotype with decreased body hair and/ or oligospermia to a typically female phenotype with primary amenorrhea and without pubic and axillary hair;
