AIM: To determine p16 promoter hypermethylation in gastric tumoral tissue and serum samples, its impact on p16-protein expression, and correlation with clinical and histological features. METHODS: Samples were obtaine...AIM: To determine p16 promoter hypermethylation in gastric tumoral tissue and serum samples, its impact on p16-protein expression, and correlation with clinical and histological features. METHODS: Samples were obtained from 52 histologically confirmed cases of gastric adenocarcinoma. Gastric tissue and serum of 50 age- and sex-matched individuals with normal gastroscopy and biopsy were obtained as control samples. Methylation-specific polymerase chain reaction (MSP) was used to evaluate methylation status of p16 promoter. p16-protein expression was analyzed by immunohistochemical staining on paraffin-embedded sections. RESULTS: Methylation was detected in 44.2% (23/52) of tumoral tissues. 60.9% of them were also methylated in serum, i.e., 26.9% of all patients (14/52). Methylation was not detected in tissue and sera of control samples. p16-protein expression was decreased in 61.5% of cases (32/52), and was significantly associated with promoter hypermethylation (P < 0.001). Methylation was significantly more frequent in higher pathological grades (P < 0.05). Methylation was not associated with other clinicopathological features and environmental factors including H pylori infection and smoking. CONCLUSION: p16 promoter hypermethylation is an important event in gastric carcinogenesis. It is the principle mechanism of p16 gene silencing. It is related to malignant tumor behavior. Detection of DNA methylation in serum may be a biomarker for early detection of gastric cancer.展开更多
<Abstract>factors,such as cigarette smoking,in esophageal squamous cell carcinoma(ESCC)in northeastern Iran,a region with a high incidence of ESCC.METHODS:The expression of p53 and p21 proteins was investigated ...<Abstract>factors,such as cigarette smoking,in esophageal squamous cell carcinoma(ESCC)in northeastern Iran,a region with a high incidence of ESCC.METHODS:The expression of p53 and p21 proteins was investigated immunohistochemically in tumor tissue from 80 ESCC patients and in 60 available paraffinembedded blocks of adjacent normal specimens from the cases,along with normal esophageal tissue from 80 healthy subjects.RESULTS:Positive expression of p53 protein was detected in 56.2%(45/80)of ESCC cases,and in none of the normal esophageal tissue of the control group(P<0.001).Furthermore,73.8%(59/80)of ESCC cases and 43.8%(35/80)of controls had positive expression of p21 protein(P<0.001).Cigarette smoking was significantly associated with p53 over-expression in ESCC cases(P=0.010,OR=3.64;95%CI:1.32-10.02).p21 over-expression was associated with poorer clinical outcome among the ESCC patients(P=0.009).CONCLUSION:Over-expression of p53 in association with cigarette smoking may play a critical role in ESCC carcinogenesis among this high-risk population of northeastern Iran.Furthermore,p21 over-expression was found to be associated with poor prognosis,specifically in the operable ESCC patients.展开更多
AIM:To investigate our clinical experience with the colonic manifestations of phosphatase and tensin homolog on chromosome ten(PTEN)hamartoma tumor syndrome(PHTS)and to perform a systematic literature review regarding...AIM:To investigate our clinical experience with the colonic manifestations of phosphatase and tensin homolog on chromosome ten(PTEN)hamartoma tumor syndrome(PHTS)and to perform a systematic literature review regarding the same.METHODS:This study was approved by the appropriate institutional review board prior to initiation.A clinical genetics database was searched for patients with PHTS or a component syndrome that received gastrointestinal endoscopy or pathology interpretation at our center.These patient’s records were retrospectively reviewed for clinical characteristics(including family history and genetic testing),endoscopy results and pathology findings.We also performed a systematic review of the literature for case series of PHTS or component syndromes that reported gastrointestinal manifestations and investigations published after consensus diagnostic criteria were established in 1996.These results were compiled and reported.RESULTS:Eight patients from our institution met initial inclusion criteria.Of these,5 patients underwent4.2 colonoscopies at mean age 45.8±10.8 years.All were found to have colon polyps during their clinical course and polyp histology included adenoma,hyperplastic,ganglioneuroma and juvenile.No malignant lesions were identified.Two had multiple histologic types.One patient underwent colectomy due to innumerable polyps and concern for future malignant potential.Systematic literature review of PHTS patients undergoing endoscopy revealed 107 patients receiving colonoscopy at mean age 37.4 years.Colon polyps were noted in92.5%and multiple colon polyp histologies were reported in 53.6%.Common polyp histologies included hyperplastic(43.6%),adenoma(40.4%),hamartoma(38.3%),ganglioneuroma(33%)and inflammatory(24.5%)polyps.Twelve(11.2%)patients had colorectal cancer at mean age 46.7 years(range 35-62).Clinical outcomes secondary to colon polyposis and malignancy were not commonly reported.CONCLUSION:PHTS has a high prevalence of colon polyposis with multiple histologic types.It should be considered a mixed polyposis syndrome.Systematic review found an increased prevalence of colorectal cancer and we recommend initiating colonoscopy for colorectal cancer surveillance at age 35 years.展开更多
We report here the characterization of a five-generation Han Chinese family with Leber's hereditary optic neuropathy (LHON). Strik- ingly, this Chinese family displayed high penetrance and expressivity of visual lo...We report here the characterization of a five-generation Han Chinese family with Leber's hereditary optic neuropathy (LHON). Strik- ingly, this Chinese family displayed high penetrance and expressivity of visual loss. The average age-of-onset of vision loss was 18 years in this family. Nineteen (11 males/8 females) of 29 matrilineal relatives in this family developed visual loss with a wide range of severity, ranging from blindness to normal vision. Sequence analysis of mitochondrial genome in this pedigree revealed the presence of the ND4 G 11778A mutation and 44 other variants belonging to Asian haplogroup M7b. The G 11778A mutation is present at homoplasmy in matri- lineal relatives of this Chinese family. Of other variants, the C01 G6480A, ND5 T12811C and Cytb A15395G located at highly conserved residues of corresponding polypeptides. In fact, these variants were implicated to be involved in other clinical abnormalities. Here, these variants may act in synergy with the primary LHON-associated Gl1778A mutation. Thus, the mitochondrial dysfunction caused by the primary ND4 G11778A mutation may be worsened by these mitochondrial variants. The results imply that the G6480A, T12811C and A15395G variants might have a potential modifier role in increasing the penetrance and expressivity of the primary LHON-associated G11778A mutation in this Chinese family.展开更多
Genetic factors play an important role in the etiology of inflammatory bowel disease(IBD). The launch of genome-wide association study(GWAS) represents a landmark in the genetic study of human complex disease. Concurr...Genetic factors play an important role in the etiology of inflammatory bowel disease(IBD). The launch of genome-wide association study(GWAS) represents a landmark in the genetic study of human complex disease. Concurrently, computational methods have undergone rapid development during the past a few years, which led to the identification of numerous disease susceptibility loci. IBD is one of the successful examples of GWAS and related analyses. A total of 163 genetic loci and multiple signaling pathways have been identified to be associated with IBD. Pleiotropic effects were found for many of these loci; and risk prediction models were built based on a broad spectrum of genetic variants. Important gene-gene, gene-environment interactions and key contributions of gut microbiome are being discovered. Here we will review the different types of analyses that have been applied to IBD genetic study, discuss the computational methods for each type of analysis, and summarize the discoveries made in IBD research with the application of these methods.展开更多
Chronic kidney disease(CKD) is a major public health problem worldwide with the estimated incidence growing by approximately 6% annually. There are striking ethnic differences in the prevalence of CKD such that, in th...Chronic kidney disease(CKD) is a major public health problem worldwide with the estimated incidence growing by approximately 6% annually. There are striking ethnic differences in the prevalence of CKD such that, in the United States, African Americans have the highest prevalence of CKD, four times the incidence of end stage renal disease when compared to Americans of European ancestry suggestive of genetic predisposition. Diabetes mel itus, hypertension and human immunodeficiency virus(HIV) infection are the major causes of CKD. HIV-associated nephropathy(HIVAN) is an irreversible form of CKD with considerable morbidity and mortality and is present predominantly in people of African ancestry. The APOL1 G1 and G2 alleles were more strongly associated with the risk for CKD than the previously examined MYH9 E1 risk haplotype in individuals of African ancestry. A strong association was reported in HIVAN, suggesting that 50% of African Americans with two APOL1 risk alleles, if untreated, would develop HIVAN. However these two variants are not enough to cause disease. The prevailing belief is that modifying factors or second hits(including genetic hits) underlie the pathogenesis of kidney disease. This work reviews the history of genetic susceptibility of CKD and outlines current theories regarding the role for APOL1 in CKD in the HIV era.展开更多
The aim of the present investigation was to study the major chromosomal aberrations (CA) like deletion, translocation, inversion and mosaic in prostate cancer patients of Tamilnadu, Southern India. Totally 45 blood sa...The aim of the present investigation was to study the major chromosomal aberrations (CA) like deletion, translocation, inversion and mosaic in prostate cancer patients of Tamilnadu, Southern India. Totally 45 blood samples were collected from various hospitals in Tamilnadu, Southern India. Equal numbers of normal healthy subjects were chosen after signing a consent form. Volunteers provided blood samples (5 ml) to establish leukocyte cultures. Cytogenetic studies were performed by using Giemsa-banding technique and finally the results were ensured by spectral karyotyping (SKY) technique. In the present investi-gation, major CA like deletion, translocation, inversion and mosaic were identified in experimental subjects. Results showed frequent CA in chromosomes 1, 3, 5, 6, 7, 9, 13, 16, 18 and X. In comparison with experimental subjects, the control subjects exhibited very low levels of major CA (P<0.05). In the present study, the high frequency of centromeric rearrangements indicates a potential role for mitotic irregularities associated with the centromere in prostate cancer tumorigenesis. Identification of chro-mosome alterations may be helpful in understanding the molecular basis of the disease in better manner.展开更多
In Indonesia,undervirilisation in 46,XY males is the most common form of difference of sex development(DSD).This can include hypospadias(misplacement of the urethra),micropenis,bifid scrotum,and undescended testis[1]....In Indonesia,undervirilisation in 46,XY males is the most common form of difference of sex development(DSD).This can include hypospadias(misplacement of the urethra),micropenis,bifid scrotum,and undescended testis[1].Undervirilisation or 46,XY DSD can be associated with a number of congenital syndromes,including Smith-Lemli-Opitz Syndrome(OMIM 602858),caused by an inborn error of cholesterol synthesis,and characterised by growth delay,intellectual disability,microcephaly,distinctive facial features,cleft palate,limb anomalies,and hypospadias[2]or Opitz syndrome(also known as Opitz G/BBB syndrome).Opitz syndrome can be caused by variants in the X-linked midline 1(MID1)gene(Type I)or in an autosomal dominant manner by monoallelic variants in sperm antigen with calponin homology and coiled-coil domains 1-like(SPECC1L)on chromosome 22q11.2(Type II)[3].Opitz syndrome is characterised by hypospadias,hypertelorism,cleft lip/palate,and heart defects[4].The prevalence of X-linked Opitz syndrome is estimated to be from 1 in 50000 to 1 in 100000 males[5].Recognition of a syndrome informs appropriate clinical management and patient care.Therefore,although these syndromes are rare,hypospadias may be diagnosed before the emergence of other comorbidities meaning that it is crucial for clinicians to perform a thorough clinical evaluation with syndromic causes in mind.展开更多
AIM: To investigate the prevalence of fragile X syndrome(FXS) in intellectually disabled male and female Indonesians.METHODS: This research is an extension of a previously reported study on the identification of chrom...AIM: To investigate the prevalence of fragile X syndrome(FXS) in intellectually disabled male and female Indonesians.METHODS: This research is an extension of a previously reported study on the identification of chromosomal aberrations in a large cohort of 527 Indonesians with intellectual disability(ID). In this previous study,87 patients had a chromosomal abnormality, five of whom expressed fragile sites on Xq27.3. Since FXS cannot always be identified by cytogenetic analysis, molecular testing of the fragile X mental retardation 1 CGG repeat was performed in 440 samples. The testing was also conducted in the five previously identified samples to confirm the abnormality. In total, a molecular study was conducted in 445 samples(162 females and 283 males).RESULTS: In the cohort of Indonesian ID population, the prevalence of FXS is 9/527(1.7%). The prevalence in males and females is 1.5%(5/329) and 2%(4/198), respectively. Segregation analysis in the families and X-inactivation studies were performed. We performed the first comprehensive genetic survey of a representative sample of male and female ID individuals from institutions and special schools in Indonesia. Our findings show that a comprehensive study of FXS can be performed in a developing country like Indonesia where diagnostic facilities are limited.CONCLUSION: The prevalence of FXS is equal in females and males in our study, which suggests that the prevalence of FXS in females could be underestimated.展开更多
The current Chemistry at Harvard Molecular Mechanics (CHARMM) force field cannot accurately describe the properties of unsaturated phospholipid membranes. In this paper, a series of simulations was performed in which ...The current Chemistry at Harvard Molecular Mechanics (CHARMM) force field cannot accurately describe the properties of unsaturated phospholipid membranes. In this paper, a series of simulations was performed in which the Lennard- Jones (L-J) parameters of lipid acyl chains of dioleoylphosphatidylcholine (DOPC) were systematically adjusted. The results showed that adjustment of the L-J parameters in lipid acyl chains can significantly improve the current CHARMM force field. It was found that the L-J parameters have different influences on the order parameters of the top half and bottom half of the chain, separated by the cis double bond. The order parameters of the top half and the bottom half of the chain are related to the area/lipid and the length of the chain, respectively.展开更多
Abnormal levels of plasma lipid have been linked to atherosclerosis, strokes and heart conditions. Variations in high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels are considered as ri...Abnormal levels of plasma lipid have been linked to atherosclerosis, strokes and heart conditions. Variations in high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels are considered as risk factors for coronary artery disease (CAD). Furthermore, triglycerides are a leading cause of cardiovascular disease. Therefore, measurement of plasma lipid levels is an important mortality predictor. Several factors were associated with irregularity in plasma lipids such as genetic alterations. Recent researches have linked single nucleotides polymorphism (SNP) in ApoA5 gene with these deviations. In this study, we reported the effects of the genetic variant c.553G>T in ApoA5 on the levels of plasma lipids. To explore these effects, a case-control study including 280 male and female subjects (44 of them were assigned as CAD cases while the remaining subjects were categorized as control) was established. All patients in the study were recruited from the western region in KSA. The results have detected minor variations in LDL, HDL and cholesterol levels between CAD patients carrying T allele and CAD patients carrying the WT allele. However, there were no significant effects due to these variations. TG levels in the wild type carriers reached up to 291 mg/dl while T allele carriers, the cases, presented lower levels of TG (170 mg/dl and 71 mg/dl). Although, T allele showed no effects on plasma lipids with the exception of TG levels. We suggest by this study that T allele in this SNP might be considered as a valuable tool in the diagnosis of CAD.展开更多
基金A grant offered by Mashhad University of Medical Sciences, No. 84129
文摘AIM: To determine p16 promoter hypermethylation in gastric tumoral tissue and serum samples, its impact on p16-protein expression, and correlation with clinical and histological features. METHODS: Samples were obtained from 52 histologically confirmed cases of gastric adenocarcinoma. Gastric tissue and serum of 50 age- and sex-matched individuals with normal gastroscopy and biopsy were obtained as control samples. Methylation-specific polymerase chain reaction (MSP) was used to evaluate methylation status of p16 promoter. p16-protein expression was analyzed by immunohistochemical staining on paraffin-embedded sections. RESULTS: Methylation was detected in 44.2% (23/52) of tumoral tissues. 60.9% of them were also methylated in serum, i.e., 26.9% of all patients (14/52). Methylation was not detected in tissue and sera of control samples. p16-protein expression was decreased in 61.5% of cases (32/52), and was significantly associated with promoter hypermethylation (P < 0.001). Methylation was significantly more frequent in higher pathological grades (P < 0.05). Methylation was not associated with other clinicopathological features and environmental factors including H pylori infection and smoking. CONCLUSION: p16 promoter hypermethylation is an important event in gastric carcinogenesis. It is the principle mechanism of p16 gene silencing. It is related to malignant tumor behavior. Detection of DNA methylation in serum may be a biomarker for early detection of gastric cancer.
基金Supported by The National Institute of Genetic Engineering and Biotechnology,Projects No.291,316Digestive Diseases Research Center of Tehran University of Medical Sciences
文摘<Abstract>factors,such as cigarette smoking,in esophageal squamous cell carcinoma(ESCC)in northeastern Iran,a region with a high incidence of ESCC.METHODS:The expression of p53 and p21 proteins was investigated immunohistochemically in tumor tissue from 80 ESCC patients and in 60 available paraffinembedded blocks of adjacent normal specimens from the cases,along with normal esophageal tissue from 80 healthy subjects.RESULTS:Positive expression of p53 protein was detected in 56.2%(45/80)of ESCC cases,and in none of the normal esophageal tissue of the control group(P<0.001).Furthermore,73.8%(59/80)of ESCC cases and 43.8%(35/80)of controls had positive expression of p21 protein(P<0.001).Cigarette smoking was significantly associated with p53 over-expression in ESCC cases(P=0.010,OR=3.64;95%CI:1.32-10.02).p21 over-expression was associated with poorer clinical outcome among the ESCC patients(P=0.009).CONCLUSION:Over-expression of p53 in association with cigarette smoking may play a critical role in ESCC carcinogenesis among this high-risk population of northeastern Iran.Furthermore,p21 over-expression was found to be associated with poor prognosis,specifically in the operable ESCC patients.
文摘AIM:To investigate our clinical experience with the colonic manifestations of phosphatase and tensin homolog on chromosome ten(PTEN)hamartoma tumor syndrome(PHTS)and to perform a systematic literature review regarding the same.METHODS:This study was approved by the appropriate institutional review board prior to initiation.A clinical genetics database was searched for patients with PHTS or a component syndrome that received gastrointestinal endoscopy or pathology interpretation at our center.These patient’s records were retrospectively reviewed for clinical characteristics(including family history and genetic testing),endoscopy results and pathology findings.We also performed a systematic review of the literature for case series of PHTS or component syndromes that reported gastrointestinal manifestations and investigations published after consensus diagnostic criteria were established in 1996.These results were compiled and reported.RESULTS:Eight patients from our institution met initial inclusion criteria.Of these,5 patients underwent4.2 colonoscopies at mean age 45.8±10.8 years.All were found to have colon polyps during their clinical course and polyp histology included adenoma,hyperplastic,ganglioneuroma and juvenile.No malignant lesions were identified.Two had multiple histologic types.One patient underwent colectomy due to innumerable polyps and concern for future malignant potential.Systematic literature review of PHTS patients undergoing endoscopy revealed 107 patients receiving colonoscopy at mean age 37.4 years.Colon polyps were noted in92.5%and multiple colon polyp histologies were reported in 53.6%.Common polyp histologies included hyperplastic(43.6%),adenoma(40.4%),hamartoma(38.3%),ganglioneuroma(33%)and inflammatory(24.5%)polyps.Twelve(11.2%)patients had colorectal cancer at mean age 46.7 years(range 35-62).Clinical outcomes secondary to colon polyposis and malignancy were not commonly reported.CONCLUSION:PHTS has a high prevalence of colon polyposis with multiple histologic types.It should be considered a mixed polyposis syndrome.Systematic review found an increased prevalence of colorectal cancer and we recommend initiating colonoscopy for colorectal cancer surveillance at age 35 years.
基金Zhejiang Provincial Natural Science Foundation(ZB0202);Chinese Young Scholar Award(No.30628013);the National Science Foundation of China to M.X.G and the Key Research and Development Program from Zhejiang Province(No.2004C14005)to J.Q.
文摘We report here the characterization of a five-generation Han Chinese family with Leber's hereditary optic neuropathy (LHON). Strik- ingly, this Chinese family displayed high penetrance and expressivity of visual loss. The average age-of-onset of vision loss was 18 years in this family. Nineteen (11 males/8 females) of 29 matrilineal relatives in this family developed visual loss with a wide range of severity, ranging from blindness to normal vision. Sequence analysis of mitochondrial genome in this pedigree revealed the presence of the ND4 G 11778A mutation and 44 other variants belonging to Asian haplogroup M7b. The G 11778A mutation is present at homoplasmy in matri- lineal relatives of this Chinese family. Of other variants, the C01 G6480A, ND5 T12811C and Cytb A15395G located at highly conserved residues of corresponding polypeptides. In fact, these variants were implicated to be involved in other clinical abnormalities. Here, these variants may act in synergy with the primary LHON-associated Gl1778A mutation. Thus, the mitochondrial dysfunction caused by the primary ND4 G11778A mutation may be worsened by these mitochondrial variants. The results imply that the G6480A, T12811C and A15395G variants might have a potential modifier role in increasing the penetrance and expressivity of the primary LHON-associated G11778A mutation in this Chinese family.
文摘Genetic factors play an important role in the etiology of inflammatory bowel disease(IBD). The launch of genome-wide association study(GWAS) represents a landmark in the genetic study of human complex disease. Concurrently, computational methods have undergone rapid development during the past a few years, which led to the identification of numerous disease susceptibility loci. IBD is one of the successful examples of GWAS and related analyses. A total of 163 genetic loci and multiple signaling pathways have been identified to be associated with IBD. Pleiotropic effects were found for many of these loci; and risk prediction models were built based on a broad spectrum of genetic variants. Important gene-gene, gene-environment interactions and key contributions of gut microbiome are being discovered. Here we will review the different types of analyses that have been applied to IBD genetic study, discuss the computational methods for each type of analysis, and summarize the discoveries made in IBD research with the application of these methods.
基金Supported by NIH Fogarty International Center Grant,No.1D43TW008330-01A1Millennium Promise Award,Noncommunicable Chronic Diseases Leadership Training Program,NHLS Research Trust,Division of Nephrology Research Fund,University of the Witwatersrand,Johannesburg and FRC Individual grant,University of the Witwatersrand,Johannesburg
文摘Chronic kidney disease(CKD) is a major public health problem worldwide with the estimated incidence growing by approximately 6% annually. There are striking ethnic differences in the prevalence of CKD such that, in the United States, African Americans have the highest prevalence of CKD, four times the incidence of end stage renal disease when compared to Americans of European ancestry suggestive of genetic predisposition. Diabetes mel itus, hypertension and human immunodeficiency virus(HIV) infection are the major causes of CKD. HIV-associated nephropathy(HIVAN) is an irreversible form of CKD with considerable morbidity and mortality and is present predominantly in people of African ancestry. The APOL1 G1 and G2 alleles were more strongly associated with the risk for CKD than the previously examined MYH9 E1 risk haplotype in individuals of African ancestry. A strong association was reported in HIVAN, suggesting that 50% of African Americans with two APOL1 risk alleles, if untreated, would develop HIVAN. However these two variants are not enough to cause disease. The prevailing belief is that modifying factors or second hits(including genetic hits) underlie the pathogenesis of kidney disease. This work reviews the history of genetic susceptibility of CKD and outlines current theories regarding the role for APOL1 in CKD in the HIV era.
文摘The aim of the present investigation was to study the major chromosomal aberrations (CA) like deletion, translocation, inversion and mosaic in prostate cancer patients of Tamilnadu, Southern India. Totally 45 blood samples were collected from various hospitals in Tamilnadu, Southern India. Equal numbers of normal healthy subjects were chosen after signing a consent form. Volunteers provided blood samples (5 ml) to establish leukocyte cultures. Cytogenetic studies were performed by using Giemsa-banding technique and finally the results were ensured by spectral karyotyping (SKY) technique. In the present investi-gation, major CA like deletion, translocation, inversion and mosaic were identified in experimental subjects. Results showed frequent CA in chromosomes 1, 3, 5, 6, 7, 9, 13, 16, 18 and X. In comparison with experimental subjects, the control subjects exhibited very low levels of major CA (P<0.05). In the present study, the high frequency of centromeric rearrangements indicates a potential role for mitotic irregularities associated with the centromere in prostate cancer tumorigenesis. Identification of chro-mosome alterations may be helpful in understanding the molecular basis of the disease in better manner.
基金Diponegoro University WCRU grant(No.118-03/UN7.6.1/PP/2021).
文摘In Indonesia,undervirilisation in 46,XY males is the most common form of difference of sex development(DSD).This can include hypospadias(misplacement of the urethra),micropenis,bifid scrotum,and undescended testis[1].Undervirilisation or 46,XY DSD can be associated with a number of congenital syndromes,including Smith-Lemli-Opitz Syndrome(OMIM 602858),caused by an inborn error of cholesterol synthesis,and characterised by growth delay,intellectual disability,microcephaly,distinctive facial features,cleft palate,limb anomalies,and hypospadias[2]or Opitz syndrome(also known as Opitz G/BBB syndrome).Opitz syndrome can be caused by variants in the X-linked midline 1(MID1)gene(Type I)or in an autosomal dominant manner by monoallelic variants in sperm antigen with calponin homology and coiled-coil domains 1-like(SPECC1L)on chromosome 22q11.2(Type II)[3].Opitz syndrome is characterised by hypospadias,hypertelorism,cleft lip/palate,and heart defects[4].The prevalence of X-linked Opitz syndrome is estimated to be from 1 in 50000 to 1 in 100000 males[5].Recognition of a syndrome informs appropriate clinical management and patient care.Therefore,although these syndromes are rare,hypospadias may be diagnosed before the emergence of other comorbidities meaning that it is crucial for clinicians to perform a thorough clinical evaluation with syndromic causes in mind.
基金Risbin-Iptekdok 2007/2008,Ministry of Health Republic of IndonesiaExcellent Scholarship(Beasiswa Unggulan Program),Foreign Scholarship(Beasiswa Luar Negeri),Directorate of Higher Education(DGHE)+1 种基金Ministry of National Education Republic of Indonesiathe PhD-fellowship Program of the Radboud University(RU-fellowship)
文摘AIM: To investigate the prevalence of fragile X syndrome(FXS) in intellectually disabled male and female Indonesians.METHODS: This research is an extension of a previously reported study on the identification of chromosomal aberrations in a large cohort of 527 Indonesians with intellectual disability(ID). In this previous study,87 patients had a chromosomal abnormality, five of whom expressed fragile sites on Xq27.3. Since FXS cannot always be identified by cytogenetic analysis, molecular testing of the fragile X mental retardation 1 CGG repeat was performed in 440 samples. The testing was also conducted in the five previously identified samples to confirm the abnormality. In total, a molecular study was conducted in 445 samples(162 females and 283 males).RESULTS: In the cohort of Indonesian ID population, the prevalence of FXS is 9/527(1.7%). The prevalence in males and females is 1.5%(5/329) and 2%(4/198), respectively. Segregation analysis in the families and X-inactivation studies were performed. We performed the first comprehensive genetic survey of a representative sample of male and female ID individuals from institutions and special schools in Indonesia. Our findings show that a comprehensive study of FXS can be performed in a developing country like Indonesia where diagnostic facilities are limited.CONCLUSION: The prevalence of FXS is equal in females and males in our study, which suggests that the prevalence of FXS in females could be underestimated.
文摘The current Chemistry at Harvard Molecular Mechanics (CHARMM) force field cannot accurately describe the properties of unsaturated phospholipid membranes. In this paper, a series of simulations was performed in which the Lennard- Jones (L-J) parameters of lipid acyl chains of dioleoylphosphatidylcholine (DOPC) were systematically adjusted. The results showed that adjustment of the L-J parameters in lipid acyl chains can significantly improve the current CHARMM force field. It was found that the L-J parameters have different influences on the order parameters of the top half and bottom half of the chain, separated by the cis double bond. The order parameters of the top half and the bottom half of the chain are related to the area/lipid and the length of the chain, respectively.
文摘Abnormal levels of plasma lipid have been linked to atherosclerosis, strokes and heart conditions. Variations in high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels are considered as risk factors for coronary artery disease (CAD). Furthermore, triglycerides are a leading cause of cardiovascular disease. Therefore, measurement of plasma lipid levels is an important mortality predictor. Several factors were associated with irregularity in plasma lipids such as genetic alterations. Recent researches have linked single nucleotides polymorphism (SNP) in ApoA5 gene with these deviations. In this study, we reported the effects of the genetic variant c.553G>T in ApoA5 on the levels of plasma lipids. To explore these effects, a case-control study including 280 male and female subjects (44 of them were assigned as CAD cases while the remaining subjects were categorized as control) was established. All patients in the study were recruited from the western region in KSA. The results have detected minor variations in LDL, HDL and cholesterol levels between CAD patients carrying T allele and CAD patients carrying the WT allele. However, there were no significant effects due to these variations. TG levels in the wild type carriers reached up to 291 mg/dl while T allele carriers, the cases, presented lower levels of TG (170 mg/dl and 71 mg/dl). Although, T allele showed no effects on plasma lipids with the exception of TG levels. We suggest by this study that T allele in this SNP might be considered as a valuable tool in the diagnosis of CAD.
文摘对浙江瑞安、福建宁德、福建东张水库3个地理群体共31例香鱼(Plecoglossus altivelis)的线粒体细胞色素b(Cyt b)基因和线粒体D-loop区序列进行了PCR扩增、序列测定、核苷酸组成和多态性分析。Cytb基因中,A、T、C和G4种核苷酸的比例分别为19.72%、29.71%、32.25%和18.32%,A+T含量为49.43%,G+C含量为50.57%。D-loop区序列中,A、T、C和G4种核苷酸的比例分别为29.99%、29.29%、23.80%和16.92%,A+T含量为59.28%,G+C含量为40.72%。在长度为1141bp的Cytb基因序列中,仅存在1个变异位点,核苷酸多样性指数(π值)为0.00028,31个样本中仅出现两种单倍型;857 bp 长的D-loop区序列中,仅存在5个变异位点,核苷酸多样性指数(π值)为0.00199,仅出现5种单倍型。这表明闽浙地区香鱼的遗传多样性水平很低,应当加大对香鱼的保护力度。