Global Medical Genetics最新文献

Comparing Genomic Profiles of ALK Fusion-Positive and ALK Fusion-Negative Nonsmall Cell Lung Cancer Patients. 比较 ALK 融合阳性和 ALK 融合阴性非小细胞肺癌患者的基因组特征

IF 1.7

Global Medical Genetics Pub Date : 2024-06-13 eCollection Date: 2024-06-01 DOI: 10.1055/s-0044-1787301

Wenchao Xia, Jing Yang, Hongbin Li, Ling Li, Jinfeng Liu

{"title":"Comparing Genomic Profiles of ALK Fusion-Positive and ALK Fusion-Negative Nonsmall Cell Lung Cancer Patients.","authors":"Wenchao Xia, Jing Yang, Hongbin Li, Ling Li, Jinfeng Liu","doi":"10.1055/s-0044-1787301","DOIUrl":"10.1055/s-0044-1787301","url":null,"abstract":"Background Anaplastic lymphoma kinase ( ALK ) fusion events account for 3 to 7% of genetic alterations in patients with nonsmall cell lung cancer (NSCLC). This study aimed to explore the landscape of ALK fusion-positive and ALK fusion-negative in a large cohort of NSCLC patients. Methods The formalin-fixed paraffin-embedded specimens of NSCLC patients who underwent next-generation sequencing from 2020 to 2023 in Yinfeng Gene Technology Co., Ltd. Clinical laboratory were included in this study. Results In the current study, a total of 180 (3.20%) patients tested positive for ALK fusions in 5,622 NSCLC samples. Within the ALK -positive cohort, a total of 228 ALK fusions were identified. Furthermore, five novel ALK fusion partners, including DAB1-ALK , KCMF1-ALK , KIF13A-ALK , LOC643770-ALK , and XDH-ALK were identified. In cases with ALK fusion-positive, TP53 alterations were the most prevalent (26.3%), followed by CDKN2A (8.4%), epidermal growth factor receptor ( EGFR , 5.6%), and ALK (5.6%). By contrast, EGFR alterations were most prevalent (51%) in patients with ALK fusion-negative NSCLC, followed by TP53 (42.7%), KRAS (11.6%), and CDKN2A (11.3%). A total of 10 cases where ALK fusion co-occurred with EGFR mutations were also identified. Notably, the ALK fusion positivity rate was higher in younger patients ( p < 0.0001) and in female patients ( p = 0.0429). Additionally, positive ALK test results were more prevalent in patients with high programmed death-ligand 1 expression, especially when applying a 50% cutoff. Conclusions Collectively, these findings offer valuable genomic insights that could inform the personalized clinical care of patients with NSCLC harboring ALK fusions within the context of precision medicine.","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11175831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141318545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinical and Molecular Characteristics of Megakaryocytes in Myelodysplastic Syndrome. 骨髓增生异常综合征中巨核细胞的临床和分子特征

IF 1.7

Global Medical Genetics Pub Date : 2024-06-10 eCollection Date: 2024-06-01 DOI: 10.1055/s-0044-1787752

Fangxiu Luo, Jialu Zhao, Yubao Chen, Zhenping Peng, Ran An, Yeling Lu, Jiaming Li

{"title":"Clinical and Molecular Characteristics of Megakaryocytes in Myelodysplastic Syndrome.","authors":"Fangxiu Luo, Jialu Zhao, Yubao Chen, Zhenping Peng, Ran An, Yeling Lu, Jiaming Li","doi":"10.1055/s-0044-1787752","DOIUrl":"10.1055/s-0044-1787752","url":null,"abstract":"Objective Myelodysplastic syndrome (MDS) is a malignant clonal disorder of hematopoietic stem cells which is characterized by morphologic dysplasia. However, the pathological characteristics of megakaryocytes (MKs) in MDS patients with gene mutation are not well established. Methods Bone marrow MK specimens from 104 patients with primary MDS were evaluated, and all patients were distributed into two groups according to gene mutation associated with functional MKs. The morphologic and cellular characteristics of MKs and platelets were recorded and compared. Results The more frequently mutated genes in MDS patients were TUBB1 (11.54%), VWF (8.65%), NBEAL2 (5.77%), and the most common point mutation was TUBB1 p.(R307H) and p.(Q43P). Patients with MK mutation showed a decrease in adenosine diphosphate-induced platelet aggregation, high proportion of CD34 + CD61 + MKs (10.00 vs. 4.00%, p = 0.012), and short overall survival (33.15 vs. 40.50 months, p = 0.013). Further, patients with a higher percent of CD34 + CD61 + MKs (≧20.00%) had lower platelet counts (36.00 × 10 9 /L vs. 88.50 × 10 9 /L, p = 0.015) and more profound emperipolesis ( p = 0.001). By analyzing RNA-sequencing of MKs, differentially expressed mRNA was involved in physiological processes including platelet function and platelet activation, especially for MDS patients with high percent of CD34 + CD61 + MKs. The high levels of expression of CD62P, CXCL10, and S100A9 mRNA, shown by RNA sequencing, were validated by PCR assay. Conclusion High proportion of CD34 + CD61 + MKs was a poor prognostic factor in MDS patients with MK mutation. CD62P, CXCL10, and S100A9 may be the potential targets to evaluate the molecular link between gene defects and platelet function.","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11164576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Laboratory-developed Droplet Digital PCR Assay for Quantification of the JAK2 V617F Mutation 实验室开发的用于定量检测 JAK2 V617F 突变的液滴数字 PCR 检测试剂盒

IF 1.7

Global Medical Genetics Pub Date : 2024-04-01 DOI: 10.1055/s-0044-1785537

Yupeng Liu, Cong Han, Jie Li, Shicai Xu, Z. Xiao, Zhiyun Guo, Shuquan Rao, Yao Yao

{"title":"Laboratory-developed Droplet Digital PCR Assay for Quantification of the JAK2 V617F Mutation","authors":"Yupeng Liu, Cong Han, Jie Li, Shicai Xu, Z. Xiao, Zhiyun Guo, Shuquan Rao, Yao Yao","doi":"10.1055/s-0044-1785537","DOIUrl":"https://doi.org/10.1055/s-0044-1785537","url":null,"abstract":"Precise quantification of the JAK2 V617F mutation using highly sensitive assays is crucial for diagnosis, treatment process monitoring, and prognostic prediction in myeloproliferative neoplasms' (MPNs) patients. Digital droplet polymerase chain reaction (ddPCR) enables precise quantification of low-level mutations amidst a high percentage of wild type alleles without the need for external calibrators or endogenous controls. The objective of this study was to optimize a ddPCR assay for detecting the JAK2 V617F mutation and establish it as a laboratory-developed ddPCR assay in our center. The optimization process involved fine-tuning five key parameters: primer/probe sequences and concentrations, annealing temperature, template amount, and PCR cycles. Our ddPCR assay demonstrated exceptional sensitivity, and the limit of quantification (LoQ) was 0.01% variant allele frequency with a coefficient of variation of approximately 76%. A comparative analysis with quantitative PCR on 39 samples showed excellent consistency (r = 0.988). In summary, through rigorous optimization process and comprehensive analytic performance validation, we have established a highly sensitive and discriminative laboratory-developed ddPCR platform for JAK2 V617F detection. This optimized assay holds promise for early detection of minimal residual disease, personalized risk stratification, and potentially more effective treatment strategies in MPN patients and non-MPN populations.","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140784387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Analysis of Factors Affecting Hematopoietic Stem Cell Mobilization Efficiency and Early Hematopoietic Reconstruction Indicators during Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation 影响自体外周血造血干细胞移植过程中造血干细胞动员效率和早期造血重建指标的因素分析

IF 1.7

Global Medical Genetics Pub Date : 2024-04-01 DOI: 10.1055/s-0044-1786006

Hao Shi, Yaya Duan, Xinting Bu

{"title":"Analysis of Factors Affecting Hematopoietic Stem Cell Mobilization Efficiency and Early Hematopoietic Reconstruction Indicators during Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation","authors":"Hao Shi, Yaya Duan, Xinting Bu","doi":"10.1055/s-0044-1786006","DOIUrl":"https://doi.org/10.1055/s-0044-1786006","url":null,"abstract":"Purpose To analyze the factors affecting the mobilization efficiency of hematopoietic stem cells and hematopoietic reconstruction indicators during autologous peripheral hematopoietic stem cell transplantation. Methods The clinical data of 54 patients who underwent autologous peripheral blood hematopoietic stem cell mobilization and transplantation at Xuzhou Central Hospital from May 2016 to April 2023 were retrospectively analyzed. The gender, age, disease type, mobilization regimen, number of chemotherapy sessions, G-CSF (granulocyte colony-stimulating factor) dosage, and platelet number at the time of collection were also collected. Moreover, the relationship between these indicators with mobilization results and hematopoietic reconstruction was analyzed. Results Results showed that age, disease type, and number of collections were significantly related to the mobilization results (number of CD34+ hematopoietic stem cells). Furthermore, multivariate analysis showed that the number of collections was an independent factor affecting mobilization efficiency. Similarly, age, platelet value at the time of collection, CD34+ stem cell value during collection, white blood cell count, and number of chemotherapy times were significantly related to the time of megakaryocytic hematopoietic reconstruction. Multifactor analysis found that age and platelet count were independent factors affecting the reconstruction time of the megakaryocytic system. However, no factor was related to the time of granulocyte hematopoietic reconstruction. Conclusion Platelet count and age when collecting hematopoietic stem cells are closely related to megakaryocytic hematopoietic reconstruction and are key indicators of early hematopoietic reconstruction after autologous hematopoietic stem cell transplantation.","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140776465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Association between Serum Lactate Dehydrogenase Level and 30-day Mortality in Patients with Intracranial Hemorrhage with Acute Leukemia in the Induction Phase: A Cohort Study 急性白血病颅内出血诱导期患者血清乳酸脱氢酶水平与 30 天死亡率的关系：队列研究

IF 1.7

Global Medical Genetics Pub Date : 2024-04-01 DOI: 10.1055/s-0044-1786005

Jia-Yuan Zhang, Zhang-Song Yan, Xiu-Juan Sun, Yong-Ze Liu, Yan-Ke Yin, Ming-Huan Su, Qiu-Ling Li, Ying-Chang Mi, Da-Peng Li

{"title":"Association between Serum Lactate Dehydrogenase Level and 30-day Mortality in Patients with Intracranial Hemorrhage with Acute Leukemia in the Induction Phase: A Cohort Study","authors":"Jia-Yuan Zhang, Zhang-Song Yan, Xiu-Juan Sun, Yong-Ze Liu, Yan-Ke Yin, Ming-Huan Su, Qiu-Ling Li, Ying-Chang Mi, Da-Peng Li","doi":"10.1055/s-0044-1786005","DOIUrl":"https://doi.org/10.1055/s-0044-1786005","url":null,"abstract":"Objectives This study aimed to identify the association between lactate dehydrogenase (LDH) levels and 30-day mortality in patients with intracranial hemorrhage (ICH) with acute leukemia during the induction phase. Methods This cohort study included patients with acute leukemia with ICH during induction. We evaluated serum LDH levels upon admission. Multivariable Cox regression analyzed the LDH 30-day mortality association. Interaction and stratified analyses based on factors like age, sex, albumin, white blood cell count, hemoglobin level, and platelet count were conducted. Results We selected 91 patients diagnosed with acute leukemia and ICH. The overall 30-day mortality rate was 61.5%, with 56 of the 91 patients succumbing. Among those with LDH levels ≥ 570 U/L, the mortality rate was 74.4% (32 out of 43), which was higher than the 50% mortality rate of the LDH < 570 U/L group (24 out of 48) ( p = 0.017). In our multivariate regression models, the hazard ratios and their corresponding 95% confidence intervals for Log2 and twice the upper limit of normal LDH were 1.27 (1.01, 1.58) and 2.2 (1.05, 4.58), respectively. Interaction analysis revealed no significant interactive effect on the relationship between LDH levels and 30-day mortality. Conclusions Serum LDH level was associated with 30-day mortality, especially in patients with LDH ≥ 570 U/L.","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140786428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prevalence and Associations of Co-occurrence of NFE2L2 Mutations and Chromosome 3q26 Amplification in Lung Cancer 肺癌中 NFE2L2 基因突变与 3q26 染色体扩增共存的发生率及相关性

IF 1.7

Global Medical Genetics Pub Date : 2024-04-01 DOI: 10.1055/s-0044-1786004

Jinfeng Liu, Sijie Liu, Dan Li, Hongbin Li, Fan Zhang

{"title":"Prevalence and Associations of Co-occurrence of NFE2L2 Mutations and Chromosome 3q26 Amplification in Lung Cancer","authors":"Jinfeng Liu, Sijie Liu, Dan Li, Hongbin Li, Fan Zhang","doi":"10.1055/s-0044-1786004","DOIUrl":"https://doi.org/10.1055/s-0044-1786004","url":null,"abstract":"Background NFE2L2 (nuclear factor erythroid-2-related factor-2) encodes a basic leucine zipper (bZIP) transcription factor and exhibits variations in various tumor types, including lung cancer. In this study, we comprehensively investigated the impact of simultaneous mutations on the survival of NFE2L2 -mutant lung cancer patients within specific subgroups. Methods A cohort of 1,103 lung cancer patients was analyzed using hybridization capture-based next-generation sequencing. Results The NFE2L2 gene had alterations in 3.0% (33/1,103) of lung cancer samples, including 1.5% (15/992) in adenocarcinoma and 16.2% (18/111) in squamous cell carcinoma. Thirty-four variations were found, mainly in exons 2 (27/34). New variations in exon 2 (p.D21H, p.V36_E45del, p.F37_E45del, p.R42P, p.E67Q, and p.L76_E78delinsQ) were identified. Some patients had copy number amplifications. Co-occurrence with TP53 (84.8%), CDKN2A (33.3%), KMT2B (33.3%), LRP1B (33.3%), and PIK3CA (27.3%) mutations was common. Variations of NFE2L2 displayed the tightest co-occurrence with IRF2 , TERC , ATR , ZMAT3 , and SOX2 ( p < 0.001). In The Cancer Genome Atlas Pulmonary Squamous Carcinoma project, patients with NFE2L2 variations and 3q26 amplification had longer median survival (63.59 vs. 32.04 months, p = 0.0459) and better overall survival. Conclusions NFE2L2 mutations display notable heterogeneity in lung cancer. The coexistence of NFE2L2 mutations and 3q26 amplification warrants in-depth exploration of their potential clinical implications and treatment approaches for affected patients.","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140767071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CRISPR-Cas9 Gene Editing: Curing Genetic Diseases by Inherited Epigenetic Modifications. CRISPR-Cas9 基因编辑：通过遗传表观遗传修饰治疗遗传疾病。

IF 1.7

Global Medical Genetics Pub Date : 2024-03-29 eCollection Date: 2024-01-01 DOI: 10.1055/s-0044-1785234

Nikhil Deep Kolanu

{"title":"CRISPR-Cas9 Gene Editing: Curing Genetic Diseases by Inherited Epigenetic Modifications.","authors":"Nikhil Deep Kolanu","doi":"10.1055/s-0044-1785234","DOIUrl":"10.1055/s-0044-1785234","url":null,"abstract":"Introduction CRISPR-Cas9 gene editing, leveraging bacterial defense mechanisms, offers precise DNA modifications, holding promise in curing genetic diseases. This review critically assesses its potential, analyzing evidence on therapeutic applications, challenges, and future prospects. Examining diverse genetic disorders, it evaluates efficacy, safety, and limitations, emphasizing the need for a thorough understanding among medical professionals and researchers. Acknowledging its transformative impact, a systematic review is crucial for informed decision-making, responsible utilization, and guiding future research to unlock CRISPR-Cas9's full potential in realizing the cure for genetic diseases. Methods A comprehensive literature search across PubMed, Scopus, and the Web of Science identified studies applying CRISPR-Cas9 gene editing for genetic diseases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria covered in vitro and in vivo models targeting various genetic diseases with reported outcomes on disease modification or potential cure. Quality assessment revealed a generally moderate to high risk of bias. Heterogeneity prevented quantitative meta-analysis, prompting a narrative synthesis of findings. Discussion CRISPR-Cas9 enables precise gene editing, correcting disease-causing mutations and offering hope for previously incurable genetic conditions. Leveraging inherited epigenetic modifications, it not only fixes mutations but also restores normal gene function and controls gene expression. The transformative potential of CRISPR-Cas9 holds promise for personalized treatments, improving therapeutic outcomes, but ethical considerations and safety concerns must be rigorously addressed to ensure responsible and safe application, especially in germline editing with potential long-term implications.","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10980556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140337123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Patterns of Cytogenomic Findings from a Case Series of Recurrent Pregnancy Loss Provide Insight into the Extent of Genetic Defects Causing Miscarriages. 从复发性妊娠流产病例系列中发现的细胞基因组学模式，有助于了解导致流产的遗传缺陷的程度。

IF 1.2

Global Medical Genetics Pub Date : 2024-03-29 eCollection Date: 2024-01-01 DOI: 10.1055/s-0044-1785227

Autumn DiAdamo, Hongyan Chai, Mei Ling Chong, Guilin Wang, Jiadi Wen, Yong-Hui Jiang, Peining Li

{"title":"Patterns of Cytogenomic Findings from a Case Series of Recurrent Pregnancy Loss Provide Insight into the Extent of Genetic Defects Causing Miscarriages.","authors":"Autumn DiAdamo, Hongyan Chai, Mei Ling Chong, Guilin Wang, Jiadi Wen, Yong-Hui Jiang, Peining Li","doi":"10.1055/s-0044-1785227","DOIUrl":"10.1055/s-0044-1785227","url":null,"abstract":"Background A retrospective study was performed to evaluate the patterns of cytogenomic findings detected from a case series of products of conception (POC) in recurrent pregnancy loss (RPL) over a 16-year period from 2007 to 2023. Results This case series of RPL was divided into a single analysis (SA) group of 266 women and a consecutive analysis (CA) group of 225 women with two to three miscarriages analyzed. Of the 269 POC from the SA group and the 469 POC from the CA group, a spectrum of cytogenomic abnormalities of simple aneuploidies, compound aneuploidies, polyploidies, and structural rearrangements/pathogenic copy number variants (pCNVs) were detected in 109 (41%) and 160 cases (34%), five (2%) and 11 cases (2%), 35 (13%) and 36 cases (8%), and 10 (4%) and 19 cases (4%), respectively. Patterns with recurrent normal karyotypes, alternating normal and abnormal karyotypes, and recurrent abnormal karyotypes were detected in 74 (33%), 71 (32%), and 80 (35%) of consecutive miscarriages, respectively. Repeat aneuploidies of monosomy X and trisomy 16, triploidy, and tetraploidy were detected in nine women. Conclusions A comparable spectrum of cytogenomic abnormalities was noted in the SA and CA groups of RPL. A skewed likelihood of 2/3 for recurrent normal and abnormal karyotypes and 1/3 for alternating normal and abnormal karyotypes in consecutive miscarriages was observed. Routine cytogenetic analysis should be performed for consecutive miscarriages. Further genomic sequencing to search for detrimental and embryonic lethal variants causing miscarriages and pathogenic variants inducing aneuploidies and polyploidies should be considered for RPL with recurrent normal and abnormal karyotypes.","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10980555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140337124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Maternal Uniparental Isodisomy of Chromosome 2 Leading to Homozygous Variants in SPR and ZNF142 : A Case Report and Review of the UPD2 Literature. 导致 SPR 和 ZNF142 同源变异的 2 号染色体母系单亲异位症：病例报告和 UPD2 文献综述。

IF 1.7

Global Medical Genetics Pub Date : 2024-03-26 eCollection Date: 2024-01-01 DOI: 10.1055/s-0044-1785442

Janhawi Kelkar, Miriam DiMaio, Deqiong Ma, Hui Zhang

{"title":"Maternal Uniparental Isodisomy of Chromosome 2 Leading to Homozygous Variants in SPR and ZNF142 : A Case Report and Review of the UPD2 Literature.","authors":"Janhawi Kelkar, Miriam DiMaio, Deqiong Ma, Hui Zhang","doi":"10.1055/s-0044-1785442","DOIUrl":"10.1055/s-0044-1785442","url":null,"abstract":"We report a 4-year-old girl with neurodevelopmental abnormalities who has maternal uniparental isodisomy of chromosome 2 leading to homozygosity for a likely pathogenic variant in SPR , and a variant of uncertain significance in ZNF142 . Biallelic pathogenic variants in SPR lead to sepiapterin reductase deficiency (SRD), a dopa-responsive dystonia. Pathogenic variants in ZNF142 are associated with an autosomal recessive neurodevelopmental disorder characterized by impaired speech and hyperkinetic movements, which has significant clinical overlap with SRD. Our patient showed dramatic improvement in motor skills after treatment with levodopa. We also reviewed 67 published reports of uniparental disomy of chromosome 2 (UPD2) associated with various clinical outcomes. These include autosomal recessive disorders associated with loci on chromosome 2, infants with UPD2 whose gestations were associated with confined placental mosaicism for trisomy 2 leading to intrauterine growth restriction with good postnatal catchup growth, and normal phenotypes in children and adults with an incidental finding of either maternal or paternal UPD2. These latter reports provide support for the conclusion that genes located on chromosome 2 are not subject to imprinting. We also explore the mechanisms giving rise to UPD2.","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10965300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140294806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Relationship between VDR Gene Polymorphisms Bsm1 and Apa1 with Breast Cancer Risk. VDR基因多态性Bsm1和Apa1与乳腺癌风险的关系

IF 1.7

Global Medical Genetics Pub Date : 2024-03-04 eCollection Date: 2024-01-01 DOI: 10.1055/s-0044-1779040

Hengameh Mozaffarizadeh, Fariborz Mokarian, Mansoor Salehi, Seyyed Mohammad Reza Hakimian, Elham Moazam, Amirmohammad Amoozadehsamakoosh, Majid Hosseinzadeh, Mahdieh Behnam, Mohaddeseh Behjati, Alma Naseri, Marzieh Lotfi, Fatemeh Tohidi

{"title":"The Relationship between VDR Gene Polymorphisms Bsm1 and Apa1 with Breast Cancer Risk.","authors":"Hengameh Mozaffarizadeh, Fariborz Mokarian, Mansoor Salehi, Seyyed Mohammad Reza Hakimian, Elham Moazam, Amirmohammad Amoozadehsamakoosh, Majid Hosseinzadeh, Mahdieh Behnam, Mohaddeseh Behjati, Alma Naseri, Marzieh Lotfi, Fatemeh Tohidi","doi":"10.1055/s-0044-1779040","DOIUrl":"10.1055/s-0044-1779040","url":null,"abstract":"Background In addition to its multifaceted physiological functions, vitamin D is recognized for its protective role against cancer. To manifest its effects, vitamin D engages with the vitamin D receptor ( VDR ) gene responsible for its encoding. Investigations have unveiled that polymorphisms within the VDR gene exert influence over the expression and/or functionality of the VDR protein. Notably, certain VDR gene polymorphisms have emerged as particularly pertinent in the context of tumorigenesis, including Fok1 (rs2228570), Bsm1 (rs1544410), Taq1 (rs771236), and Apa1 (rs7975232). This study aims to scrutinize the correlation between the Bsm1 and Apa1 polymorphisms and the susceptibility to breast cancer development. Materials and Methods In this study, 50 patients suffering from breast cancer with less than 6 months breast cancer diagnosis and 50 healthy control individuals have been chosen. Restriction fragment length polymorphism polymerase chain reaction was used to determine the genotype of polymorphisms. Results The results of the statistical analysis showed that among the studied polymorphisms, there was no correlation with the development of breast cancer. Conclusion Studies on various cancers have produced inconsistent results regarding vitamin D's role in the development and progression of cancer. Therefore, further research is necessary to determine vitamin D's role in cancer development and progression.","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10911907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140029179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0