Pharmacogenomics & Personalized Medicine最新文献

{"title":"Apolipoprotein E Gene Polymorphism Effects on Lipid Metabolism and Risk of Cerebral Infarction in Northwest Han Chinese Population.","authors":"Yaqi Wang,&nbsp;Shuang Yang,&nbsp;Suya Zhang,&nbsp;Xiaoyu Lu,&nbsp;Wenbing Ma","doi":"10.2147/PGPM.S404663","DOIUrl":"https://doi.org/10.2147/PGPM.S404663","url":null,"abstract":"<p><strong>Background: </strong>The apolipoprotein E (ApoE) genetic variation may contribute to the development of Cerebral Infarction (CI). Serum lipid levels are known risk factors for CI, but the effect of the ApoE gene polymorphism on lipid metabolism remains unclear. This retrospective cohort study was designed to determine the role of ApoE genotypes in CI risk and the relationships between ApoE gene polymorphism and serum lipid levels among the population of northwest China.</p><p><strong>Patients and methods: </strong>517 CI patients and 517 non-CI controls were enrolled in the study. Polymerase chain reaction and hybridization were utilized to determine the ApoE gene polymorphisms.</p><p><strong>Results: </strong>The ε3/ε4 genotype and ε4 allele frequency were significantly higher in CI patients than in controls. When stratified by age and sex, statistically significant differences in the distribution and frequency of the ε3/ε4 genotype and ε4 allele were found between patients and controls. Compared to ε2 carriers, ε4 carriers had significantly lower ApoE levels and higher low-density lipoprotein cholesterol (LDL-C), ApoB and ApoB/ApoA-I levels in both two groups. Additionally, control participants with ε4 carriers had significantly higher levels of lipoprotein and total cholesterol (TC) levels than ε2 carriers, while CI patients with ε4 carriers had a significantly lower level of ApoA-I. After adjusting for other established risk factors, drinking, hypertension, lipoprotein, triglycerides (TG) and ε4 allele were significant independent risk factors for CI, which was shown to be associated with a nearly two-fold CI risk.</p><p><strong>Conclusion: </strong>This study demonstrated that ε4 allele is independent risk factors for CI among patients in Northwest China. ApoE polymorphism was associated with CI, which was partly mediated through blood lipids and may also be mediated through non-lipid pathways. These data might be of great clinical significance in individualized preventive and therapeutic strategies.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"303-312"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c1/2a/pgpm-16-303.PMC10083142.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9304360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Transporter Associated with Antigen Processing 1</i> Gene Polymorphisms Increase the Susceptibility to Tuberculosis.","authors":"Tianchang Lu,&nbsp;Minyi Wang,&nbsp;Nannan Liu,&nbsp;Shuqiong Zhang,&nbsp;Lei Shi,&nbsp;Ling Bao,&nbsp;Feng Luo,&nbsp;Li Shi,&nbsp;Shuyuan Liu,&nbsp;Yufeng Yao","doi":"10.2147/PGPM.S404339","DOIUrl":"https://doi.org/10.2147/PGPM.S404339","url":null,"abstract":"<p><strong>Purpose: </strong>Tuberculosis (TB) is known to result from a complex interaction between the host immune response and <i>Mycobacterium</i> infection. The transporter associated with antigen processing (TAP) plays an important role in the processing and presentation pathways for the <i>Mycobacterium tuberculosis</i> (<i>M. tb</i>) antigen. To investigate the possible association of the <i>TAP1</i> and <i>TAP2</i> genes with TB.</p><p><strong>Patients and methods: </strong>A total of 449 TB patients and 435 control subjects were included in this study, and single nucleotide polymorphisms (SNPs) in the <i>TAP</i> gene, as well as <i>TAP1</i> and <i>TAP2</i> alleles, were genotyped.</p><p><strong>Results: </strong><i>TAP</i> gene association analysis of TB diseases showed that rs41551515-T in the <i>TAP1</i> gene was significantly associated with susceptibility to TB (<i>P</i>=7.96E-04, OR=4.124, 95% CI: 1.683-10.102), especially pulmonary TB (PTB, <i>P</i>=6.84E-04, OR=4.350, 95% CI: 1.727-10.945), and the combination of rs1057141-T-rs1135216-C in the <i>TAP1</i> gene significantly increased the risk of TB susceptibility (<i>P</i>=5.51E-05, OR=10.899, 95% CI: 2.555-46.493). Five novel <i>TAP1</i> alleles were detected in Yunnan Han people, and the allele frequency of <i>TAP1*unknown_3</i> (rs41555220-rs41549617-rs1057141-rs1135216-rs1057149-rs41551515: C-A-T-C-C-T) was notably increased in all TB patients, including in the PTB and EPTB subgroups, and was significantly associated with the risk of susceptibility to TB. However, no association between the <i>TAP2</i> gene and TB was found in this study.</p><p><strong>Conclusion: </strong>Host genetic variants of rs41551515-T and the combination rs1057141-T-rs1135216-C, as well as <i>TAP1*unknown_3</i> may play a critical role in susceptibility to TB disease.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"325-336"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/83/c0/pgpm-16-325.PMC10108862.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9389942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction and Validation of a Novel Nomogram for Predicting the Recurrence of Diffuse Large B Cell Lymphoma Treated with R-CHOP.","authors":"Yuxi Gong,&nbsp;Haitao Yan,&nbsp;Yefan Yang,&nbsp;Boya Zhai,&nbsp;Zhendong Huang,&nbsp;Zhihong Zhang","doi":"10.2147/PGPM.S399336","DOIUrl":"https://doi.org/10.2147/PGPM.S399336","url":null,"abstract":"<p><strong>Purpose: </strong>To explore recurrence-risk factors of diffuse large B cell lymphoma (DLBCL) and construct a risk nomogram for predicting recurrence.</p><p><strong>Patients and methods: </strong>A retrospective analysis was performed on 228 DLBCL patients who achieved complete remission after R-CHOP treatment between January 2015 and December 2019. Univariate and multivariate analyses were applied to identify recurrence-related risk factors from the pretreatment evaluation factors covering patients' demographic characteristics, clinical manifestations, serological indicators, pathological and immunohistochemical results. A nomogram was developed based on the above results and validated by the concordance index (C-index), the receiver operating characteristic (ROC) curve, and the calibration curve.</p><p><strong>Results: </strong>The training and validation cohorts consisted of 160 and 68 patients (randomized by 7:3). Of the whole cohort, 50 of 228 (21.9%) cases recurred during follow-up. Three recurrence-risk factors including BCL2 expression (P = 0.027), CD10 expression (P = 0.021), LDH level (P = 0.004) were identified from multivariate analysis and entered the final nomogram. The C-index of the nomogram was 0.815 in training cohort and 0.797 in the validation cohort, higher than that of IPI system (0.699) and NCCN-IPI system (0.709). And the 1-year, 2-year, 3-year, and 4-year areas under ROC (AUC) were 0.812, 0.850, 0.837, and 0.801, respectively. The calibration curves also showed a good discrimination capability and accuracy.</p><p><strong>Conclusion: </strong>The novel nomogram incorporating the three independent risk factors (BCL2 expression, CD10 expression and LDH level) provided a valuable tool for predicting DLBCL recurrence.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"291-301"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3e/7d/pgpm-16-291.PMC10075220.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9273291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotypic and Phenotypic Composition of Sickle Cell Disease in the Arab Population - A Systematic Review.","authors":"Fateen Ata,&nbsp;Alaa Rahhal,&nbsp;Lujain Malkawi,&nbsp;Phool Iqbal,&nbsp;Ibrahim Khamees,&nbsp;Mousa Alhiyari,&nbsp;Zohaib Yousaf,&nbsp;Hana Qasim,&nbsp;Awni Alshurafa,&nbsp;Sundus Sardar,&nbsp;Saad Javed,&nbsp;Liam Fernyhough,&nbsp;Mohamed Yassin","doi":"10.2147/PGPM.S391394","DOIUrl":"https://doi.org/10.2147/PGPM.S391394","url":null,"abstract":"<p><p>Sickle cell disease (SCD) is a genetic disease influenced by ethnicity and regional differences in its clinical course. Recent advances in the management of SCD with newer therapies are being introduced to the Western population. However, many of these treatments are yet to be used in the Arabic SCD population. Understanding the genetic variations of SCD regionally is essential to anticipate the utilization of new treatments. This systematic review's main objective is to pool the available data on the genetic composition of SCD in the Arabic population. Data for 44,034 patients was extracted from 184 studies (11 case reports, 8 case series, 56 retrospectives, 107 prospective observational studies, and 2 clinical trials) using PubMed, Scopus, and Google Scholar. Male (49%) and female (51%) patients were equally reported wherever gender was available (N=13105). Various SCD genotypes were reported in a total of 14,257 patients, including Hb SS (77%) Hb Sβ0 (9.9%), and Hb Sβ+ (7.2%), while the rest of the genotypes, including HbSC, HbSD, HbSE, HbSO Arab, Hb S/α-Thal, Hb Sβ0 + α-Thal, and HBS Oman were individually reported in <4% of the cases. Major SCD complications in the Arab population included pain crises (48.25%) followed by neurological complications (33.46%), hepatobiliary complications (25.53%), musculoskeletal complications (24.73%), and hemolytic anemia (23.57%). The treatments reported for SCD included hydroxyurea (20%), blood transfusion (14.32%), and Deferasirox (3.03%). We did not find the use of stem cell transplantation or newer treatments such as L-Glutamine, Voxelotor, Crizanlizumab, or gene therapy reported in any of the studies included in our review. This review highlights the genetic makeup of SCD in Arab countries and its common phenotypic manifestations and will help direct further research on SCD in this region, especially concerning genetic therapy.</p><p><strong>Systematic review registration: </strong>The protocol has been registered in the International Prospective Register of Systematic Reviews(PROSPERO):CRD42020218,666. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=218666.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"133-144"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9961577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9352670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MTHFR and MTRR Genetic Polymorphism of Methotrexate Therapy Outcomes in Early Rheumatoid Arthritis.","authors":"Qian Zhang,&nbsp;Pan Fu,&nbsp;Zhanglei Cao,&nbsp;Hua Huang,&nbsp;Qinwen Wen,&nbsp;Kaizhe Wang,&nbsp;Tong Kong,&nbsp;Xiudi Wu,&nbsp;Jianping Zheng","doi":"10.2147/PGPM.S404949","DOIUrl":"https://doi.org/10.2147/PGPM.S404949","url":null,"abstract":"<p><strong>Purpose: </strong>Methotrexate (MTX) is used as an anchor drug for the treatment of rheumatoid arthritis (RA) and there may be differences in drug action between genotypes. The purpose of this study was to investigate the relationship between clinical efficacy response and disease activity of MTX monotherapy with methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms.</p><p><strong>Patients and methods: </strong>In the study, a population of 32 patients in East China with early RA fulfilling the diagnostic standards of the American College of Rheumatology (ACR) were enrolled, all of them received MTX monotherapy. Genotyping of patients MTHFR C677T and A1298C, MTRR A66G using tetra-primer ARMS-PCR method and sanger sequencing to verify its accuracy.</p><p><strong>Results: </strong>The distribution of three polymorphic genotypes that were studied is in accordance with the Hardy-Weinberg genetic equilibrium. The patient pathology variables smoke (OR = 0.088, P = 0.037), drink alcohol (OR = 0.039, P = 0.016) and males (OR = 0.088, P = 0.037) were significantly associated with non-response to MTX. Genotype, allele distribution and genetic statistical models were not found to be related to MTX treatment response and disease activity in both the response groups and non-response groups.</p><p><strong>Conclusion: </strong>Our findings suggest that the MTHFR C677T, MTHFR A1298C and MTRR A66G polymorphisms may not predict MTX clinical treatment response and disease activity in patients with early RA. The study revealed that smoke, alcohol, and males were possible influential factors for MTX non-response.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"407-423"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2a/a0/pgpm-16-407.PMC10163902.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9436402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration and Validation of Pancreatic Cancer Hub Genes Based on Weighted Gene Co-Expression Network Analysis and Immune Infiltration Score Analysis.","authors":"Xiao-Xi Li,&nbsp;Hong Li,&nbsp;Li-Quan Jin,&nbsp;Yun-Bo Tan","doi":"10.2147/PGPM.S403116","DOIUrl":"https://doi.org/10.2147/PGPM.S403116","url":null,"abstract":"<p><strong>Objective: </strong>To find pancreatic cancer (PC)-related hub genes based on weighted gene co-expression network analysis (WGCNA) construction and immune infiltration score analysis and validate them immunohistochemically by clinical cases, to generate new concepts or therapeutic targets for the early diagnosis and treatment of PC.</p><p><strong>Material and methods: </strong>In this study, WGCNA and immune infiltration score were utilized to identify the relevant core modules of PC and the hub genes within these core modules.</p><p><strong>Results: </strong>Using WGCNA analysis, data from PC and normal pancreas integrated with TCGA and GTEX were analyzed and brown modules were chosen from the six modules. Five hub genes, including DPYD, FXYD6, MAP6, FAM110B, and ANK2, were discovered to have differential survival significance via validation tests utilizing survival analysis curves and the GEPIA database. The DPYD gene was the only gene associated with PC survival side effects. Validation of the Human Protein Atlas (HPA) database and immunohistochemical testing of clinical samples showed positive results for DPYD expression in PC.</p><p><strong>Conclusion: </strong>In this study, we identified DPYD, FXYD6, MAP6, FAM110B, and ANK2, as immune-related candidate markers for PC. Only the DPYD gene had a negative impact on the survival of PC patients. Through validation of the HPA database and immunohistochemical testing of clinical cases, we believe that the DPYD gene brings novel ideas and therapeutic targets in the diagnosis and treatment of PC.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"467-480"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6b/8a/pgpm-16-467.PMC10216855.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9548037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of <i>TREM1</i> Variants on the Risk and Prognosis of Glioma in the Chinese Han Population.","authors":"Mingjun Hu,&nbsp;Jie Wei,&nbsp;Jie Hao,&nbsp;Tianbo Jin,&nbsp;Bin Li","doi":"10.2147/PGPM.S403870","DOIUrl":"https://doi.org/10.2147/PGPM.S403870","url":null,"abstract":"<p><strong>Background: </strong>Glioma is the main pathological subtype of brain tumors with high mortality.</p><p><strong>Objective: </strong>This study aimed to elucidate the correlation between <i>TREM1</i> variants and glioma risk in the Chinese Han population.</p><p><strong>Methods: </strong>Genotyping of six variants of <i>TREM1</i> was completed by Agena MassARRAY platform in 1061 subjects (503 controls and 558 glioma patients). The relationship between <i>TREM1</i> polymorphisms and glioma risk was calculated using the logistic regression model, with odds ratio (OR) and 95% confidence intervals (CIs). A multifactor dimensionality reduction (MDR) method was performed to assess SNP-SNP interactions to predict glioma risk.</p><p><strong>Results: </strong>In this research, overall analysis illustrated an association between <i>TREM1</i> rs9369269 and an increased risk of glioma. Rs9369269 was also related to the risk of glioma in patients aged ≤40 years and females. Subjects with rs9369269 AC genotype were likely to obtain glioma compared to people with CC genotype (patients with astroglioma vs healthy people). Compared to TT genotype carriers, carriers with AT genotype of rs1351835 were significantly associated with overall survival (OS).</p><p><strong>Conclusion: </strong>Taken together, the study identified the association between <i>TREM1</i> variants and glioma risk and <i>TREM1</i> variants were significantly associated with the prognosis of glioma. In the future, larger samples are needed to verify the results.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"707-715"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cb/1d/pgpm-16-707.PMC10327902.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9808389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hsa_circ_0003489 Drives PTX Resistance of Human NSCLC Cells Through Modulating miR-98-5p/IGF2.","authors":"Shaofeng Xia,&nbsp;Chenliang Wang","doi":"10.2147/PGPM.S416360","DOIUrl":"https://doi.org/10.2147/PGPM.S416360","url":null,"abstract":"<p><strong>Background: </strong>Circular RNAs (circRNAs) demonstrated critical roles within developing tumors and treatment resistance in an increasing body of research. The aim was to look into the functions and processes of hsa_circ_0003489 in the non-small cell lung cancer (NSCLC) paclitaxel (PTX) resistance.</p><p><strong>Methods: </strong>NSCLC cell-based cultures including A549 and H460 were employed for such an investigation. hsa_circ_0003489, miR-98-5p, and insulin-like growth factor 2 (IGF2) expression-profiles were evaluated with a quantitative real-time polymerase chain reaction (RT-qPCR). The PTX resistance was determined using MTT assay, and the ELISA test measured IGF2 expression. Facilitating corroboration for miR-98-5p relation and hsa_circ_0003489 or IGF2, a dual-luciferase reporter method was applied.</p><p><strong>Results: </strong>The hsa_circ_0003489 level was raised in cells and tissues from PTX-resistant (PR) NSCLC. In PR NSCLC cells, hsa_circ_0003489 knockdown reduced PTX resistance. For the purpose of the mechanism study, hsa_circ_0003489 knockdown substantially reduced IGF2 expression via miR-98-5p sponging, improving PTX sensitivity in PR NSCLC.</p><p><strong>Conclusion: </strong>Through miR-98-5p/IGF2 axis control, hsa_circ_0003489 knockdown helped NSCLC overcome PTX resistance, suggesting a potential circRNA-targeted therapy for the disease.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"805-815"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/88/de/pgpm-16-805.PMC10488782.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10218680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and Gene Analysis of Fatty Acid Oxidation Disorders Found in Neonatal Tandem Mass Spectrometry Screening.","authors":"Xiaoxia Wang,&nbsp;Haining Fang","doi":"10.2147/PGPM.S402760","DOIUrl":"https://doi.org/10.2147/PGPM.S402760","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the clinical and gene mutation characteristics of fatty acid oxidative metabolic diseases found in neonatal screening.</p><p><strong>Methods: </strong>A retrospective analysis was performed on 29,948 neonatal blood tandem mass spectrometry screening samples from January 2018 to December 2021 in our neonatal screening centre. For screening positive, recall review is still suspected of fatty acid oxidation metabolic disorders in children as soon as possible to improve the genetic metabolic disease-related gene detection package to confirm the diagnosis. All diagnosed children were followed up to the deadline.</p><p><strong>Results: </strong>Among 29,948 neonates screened by tandem mass spectrometry, 14 cases of primary carnitine deficiency, six cases of short-chain acyl coenzyme A dehydrogenase deficiency, two cases of carnitine palmitoyltransferase-I deficiency and one case of multiple acyl coenzyme A dehydrogenase deficiency were recalled. Except for two cases of multiple acyl coenzyme A dehydrogenase deficiency that exhibited [manifestations], the other 21 cases were diagnosed pre-symptomatically. Eight mutations of <i>SLC22A</i>5 gene were detected, including c.51C>G, c.403G>A, c.506G>A, c.1400C>G, c.1085C>T, c.706C>T, c.1540G>C and c.338G>A. Compound heterozygous mutation of <i>CPT1A</i> gene c.2201T>C, c.1318G>A, c.2246G>A, c.2125G>A and ETFA gene c.365G>A and c.699_701delGTT were detected, and new mutation sites were found.</p><p><strong>Conclusion: </strong>Neonatal tandem mass spectrometry screening is an effective method for identifying fatty acid oxidative metabolic diseases, but it should be combined with urine gas chromatography-mass spectrometry and gene sequencing technology. Our findings enrich the gene mutation profile of fatty acid oxidative metabolic disease and provide evidence for genetic counselling and prenatal diagnosis in families.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"577-587"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d1/c0/pgpm-16-577.PMC10254624.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9618148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Characteristics and Novel <i>ZEB2</i> Gene Mutation Analysis of Three Chinese Patients with Mowat-Wilson Syndrome.","authors":"Xiao Han,&nbsp;Qianjuan Zhang,&nbsp;Chengcheng Wang,&nbsp;Bingjuan Han","doi":"10.2147/PGPM.S414161","DOIUrl":"https://doi.org/10.2147/PGPM.S414161","url":null,"abstract":"<p><strong>Purpose: </strong>Mowat-Wilson syndrome (MWS) is an autosomal dominant disease caused by a pathogenic variant of the <i>ZEB2</i> gene. The main clinical manifestations include special facial features, Hirschsprung disease (HSCR), global developmental delay and other congenital malformations. Here, we summarize the clinical characteristics and genetic mutation analysis of three Chinese patients with MWS.</p><p><strong>Patients and methods: </strong>The clinical characteristics of the patients were monitored and the treatment effect was followed up. DNA was extracted from peripheral blood and analyzed by sequencing. Whole exome sequencing was then performed.</p><p><strong>Results: </strong>Three novel <i>ZEB2</i> gene mutations were identified in 3 patients (c.1147_1150dupGAAC, p.Q384Rfs*7, c.1137_1146del TAGTATGTCT, p.S380Nfs *13 and c.2718delT, p.A907Lfs*23). They all had special facial features, intellectual disability, developmental delay, microcephaly, structural brain abnormalities and other symptoms. After long-term regular rehabilitation treatment, the development quotient of each functional area of the patient was slightly improved.</p><p><strong>Conclusion: </strong>Our study expanded the mutation spectrum of ZEB2 and enriched our understanding of the clinical features of MWS. It also shows that long-term standardized treatment is of great significance for the prognosis of patients.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"777-783"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/02/b6/pgpm-16-777.PMC10460601.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10166636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}