中华医学遗传学杂志最新文献

{"title":"[Serological characteristics and bioinformatics analysis of 4 blood donors with RHCE*cE(281C,282T) variant allele].","authors":"Fan Wu, Naibao Zhuang, Liyan Sun, Tong Liu, Yanlian Liang, Shuang Liang","doi":"10.3760/cma.j.cn511374-20240828-00458","DOIUrl":"https://doi.org/10.3760/cma.j.cn511374-20240828-00458","url":null,"abstract":"<p><strong>Objective: </strong>To explore the serological characteristics and bioinformatics analysis results of 4 blood donors with RHCE*cE(281C, 282T) variant allele.</p><p><strong>Methods: </strong>A total of 4 non-related blood donors with RHCE*cE (281C, 282T) variant allele (donors 1-4) were selected as the study objects. They donated blood at Shenzhen Blood Center from January 2022 to June 2023. The 4 blood donors were all Han. And 5 mL elbow venous blood was collected from these 4 blood donors. Regular serological assaying with 4 kinds of monoclonal antibody reagents was used for determination of the RhCcEe type. The nucleotide sequences of all 10 exons and adjacent flanking intron regions of RHCE gene in these 4 donors were analyzed by Sanger sequencing, and the full-length haplotype analysis of RHCE gene was performed by using the single-molecule real-time sequencing (SMRT) third-generation technology. DeepTMHMM software was used to analyze the structure of protein transmembrane region of wild type and variant RhCcEe protein and predict the location of amino acid substitution. The effects of mutations on RhCcEe protein function were analyzed using PolyPhen-2, SIFT and Mutation Taster bioinformatics software. Robetta and Swiss-PdbViewer v4.1.0 were used for modeling the tertiary structures of RhCcEe to analyze the difference between wild type and variant RhCcEe protein. The mutation was rated according to the standards and guidelines for the classification of genetic variants of the American College of Medical Genetics and Genomics (ACMG). This study has been approved by the Medical Ethics Committee of Shenzhen Blood Center (Approval No. SZBCMEC-2022-024).</p><p><strong>Results: </strong>The RhCcEe phenotypes of the 4 blood donors were CCEweake by serological assaying. The RhE antigen were weakly expressed form 0 to 3+. The analysis of RHCE gene sequence indicated that all the 4 donors with RHCE*cE (281C, 282T) allele. The mutation caused the substitution of a single amino acid in the RhCcEe protein (p.Leu94 Pro) and the amino acid substitution was located in the transmembrane α3 chain resulted in significant changes in the 3D structure of the extracellular region of RhCcEe protein. The substitution was predicted to be \"Probably damaging\", \"Damaging\" and \"Polymorphism\" by PolyPhen-2, SIFT and Mutation Taster bioinformatics software. According to the guidelines of ACMG, the variant was rated to be likely pathogenic.</p><p><strong>Conclusion: </strong>The RHCE*cE (281C, 282T) variant allele was first found in the Han Chinese population. The serological data of this allele were enriched. It provides an important guarantee for the safety of blood transfusion. Bioinformatics analysis provided evidences for further study of the structure and functions of RhCcEe protein.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 2","pages":"137-144"},"PeriodicalIF":0.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023228","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}

{"title":"[Analysis of hematological characteristics of patients with three common deletional β-thalassemias and concomitant α-thalassemia in Huizhou, Guangdong province].","authors":"Zhiyang Guan, Dina Chen, Zeyan Zhong, Zhiyong Wu, Guoxing Zhong, Shaohui Huang, Jianhong Chen","doi":"10.3760/cma.j.cn511374-20241013-00570","DOIUrl":"https://doi.org/10.3760/cma.j.cn511374-20241013-00570","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To analyze the hematological characteristics of patients with three common deletional β-thalassemia and concomitant α-thalassemia in Huizhou, Guangdong province.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A total of 1 335 subjects of childbearing age with hemoglobin F (Hb F) ≥ 5% at the Huizhou First Maternal and Child Health Care Hospital between June 2014 and December 2023 were enrolled as our study cohort. The hematological parameters were determined by blood cell counters and automatic capillary electrophoresis, while liquid phase chip and gap-PCR were employed for the detection of routine thalassemias and the three common deletional β-thalassemia, respectively. The hematological characteristics of patients with the deletional β-thalassemia were analyzed. This study was reviewed and approved by the Ethics Committee of Huizhou First Maternal and Child Health Care Hospital [Ethics No. 20231107(B2)].&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 384 cases of the three common deletional β-thalassemia were identified, including 184 cases of Chinese Gγ&lt;sup&gt;+&lt;/sup&gt;(Aγδβ)&lt;sup&gt;0&lt;/sup&gt;, 191 cases of Southeast Asian hereditary persistence of fetal hemoglobin (SEA-HPFH), and nine cases of Chinese Taiwanese, for a total detection rate of 28.76%. Patients who did not meet the established criteria were excluded from the study, leaving 372 cases. All of which presented with hypochromic microcytic anemia and significantly elevated Hb F. Except for normal or decreasing of Hb A2 levels in patients with Chinese Gγ&lt;sup&gt;+&lt;/sup&gt;(Aγδβ)&lt;sup&gt;0&lt;/sup&gt;, the levels of Hb A2 in patients with the other two deletional β-thalassemia were increased with different degrees. Differential comparison results showed that significant differences were observed in Hb A2 and Hb F values among the groups of the three common deletional β-thalassemia heterozygotes (P &lt; 0.05). According to the type of gene variation, 180 patients with Chinese Gγ&lt;sup&gt;+&lt;/sup&gt;(Aγδβ)&lt;sup&gt;0&lt;/sup&gt; heterozygotes were divided into three groups, including αα/αα, Chinese Gγ&lt;sup&gt;+&lt;/sup&gt;(Aγδβ)&lt;sup&gt;0&lt;/sup&gt;/β&lt;sup&gt;N&lt;/sup&gt; (149), -α/αα, Chinese Gγ&lt;sup&gt;+&lt;/sup&gt;(Aγδβ)&lt;sup&gt;0&lt;/sup&gt;/β&lt;sup&gt;N&lt;/sup&gt; (14), and --/αα, Chinese Gγ&lt;sup&gt;+&lt;/sup&gt;(Aγδβ)&lt;sup&gt;0&lt;/sup&gt;/β&lt;sup&gt;N&lt;/sup&gt; (17). Similarly, 179 patients with SEA-HPFH heterozygotes were divided into three groups, including αα/αα, SEA-HPFH/β&lt;sup&gt;N&lt;/sup&gt; (150), -α/αα, SEA-HPFH/β&lt;sup&gt;N&lt;/sup&gt; (12), and --/αα, SEA-HPFH/β&lt;sup&gt;N&lt;/sup&gt; (17). Differential comparison results showed that the Hb F levels of the Chinese Gγ&lt;sup&gt;+&lt;/sup&gt;(Aγδβ)&lt;sup&gt;0&lt;/sup&gt; combined with α&lt;sup&gt;0&lt;/sup&gt;-thalassemia group were significantly lower than those of the Chinese Gγ&lt;sup&gt;+&lt;/sup&gt;(Aγδβ)&lt;sup&gt;0&lt;/sup&gt; combined with α&lt;sup&gt;+&lt;/sup&gt;-thalassemia group and the control group (P &lt; 0.05). The mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and Hb F values of the SEA-HPFH combined with α&lt;sup&gt;0&lt;/sup&gt;-thalassemia group were significantly lower than those of the SEA-HPFH combined with α&lt;sup&gt;+&lt;/sup&gt;-","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 2","pages":"129-136"},"PeriodicalIF":0.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043674","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}

{"title":"[Prenatal phenotype and genetic analysis of two fetuses with Bardet-Biedl syndrome].","authors":"Lingyi Zhang, Zhigang Zhang, Xingguang Wang, Yanyan Li","doi":"10.3760/cma.j.cn511374-20241019-00545","DOIUrl":"https://doi.org/10.3760/cma.j.cn511374-20241019-00545","url":null,"abstract":"<p><strong>Objective: </strong>To carry out genetic testing on two fetuses with prenatal ultrasound finding of polydactyly and renal abnormalities to determine the underlying causes.</p><p><strong>Methods: </strong>Two fetuses with structural abnormalities detected by prenatal ultrasound at Cangzhou People's Hospital in 2021 were selected as the study subjects. Genomic DNA was extracted from the muscle tissue of the abortus and peripheral blood samples from both parents. Whole-exome sequencing (WES) was conducted on the trio to detect the genetic variants. Quantitative PCR was used to validate the exonic deletions. This study has been approved by the Ethics Committee of Cangzhou People's Hospital (Ethics No.K2020-049).</p><p><strong>Results: </strong>Prenatal ultrasound revealed postaxial polydactylies of fingers and toes and slightly enlarged kidneys with increased echogenicity in fetus 1, along with polydactyly of both hands, enlarged kidneys, and enhanced echogenicity of renal parenchyma in fetus 2. Trio-WES analysis revealed that fetus 1 has harbored a pathogenic c.1339G>A variant of the BBS1 gene, along with a heterozygous 426 bp deletion in the 11q13.2 region, which was unreported previously. The deletion has involved exons 10 and 11 of the BBS1 gene. The two variants were inherited from its mother and father, respectively. Fetus 2 was found to harbor a pathogenic c.539G>A variant and a likely pathogenic c.49G>A variant of the BBS10 gene, which were inherited from its mother and father, respectively. The c.49G>A variant has not been documented in databases and the literature.</p><p><strong>Conclusion: </strong>Two rare fetuses with Bardet-Biedl syndrome have been diagnosed. Above finding has expanded the mutational spectrum of this syndrome and has important implications for genetic counseling for the affected families.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 2","pages":"226-231"},"PeriodicalIF":0.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051370","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}

{"title":"[Identification of Jr(a-) rare blood type antibodies against anti-Jra: serological and molecular biology analysis and transfusion strategy].","authors":"Yunxiang Wu, Hua Wang, Ruiqing Guo, Zhicheng Li, Qing Li, Dong Xiang, Yanli Ji, Aijing Li, Fengyong Zhao, Fei Wang, Jiangtao Zuo, Yi Xu, Yajun Liang, Demei Zhang","doi":"10.3760/cma.j.cn511374-20240930-00515","DOIUrl":"https://doi.org/10.3760/cma.j.cn511374-20240930-00515","url":null,"abstract":"<p><strong>Objective: </strong>To report the blood group antigen and antibody specificity identification methods for a patient with high-frequency antibodies, and the process of finding and providing compatible blood for the patient.</p><p><strong>Methods: </strong>A patient sent from the Blood Transfusion Department of Shanxi Provincial People's Hospital to Blood Transfusion Technology Research Laboratory of Taiyuan Blood Center in November 2022 was selected for the study. Classical serological methods were used to determine the patient's blood type, screen for unexpected antibodies, identify antibodies, and perform crossmatching. High-frequency antibody identification was carried out using red blood cells treated with various enzymes. Blood group genotyping was conducted using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF) and Sanger sequencing. Multiple strategies were employed to address the patient's blood source problem. The study was approved by the Medical Ethics Committee of Taiyuan Blood Center [Ethics No. 2024 Ethics Review No.(2)].</p><p><strong>Results: </strong>The patient's blood type was B, RhD positive. Initial screening of the patient's serum with multiple screening cells and antibody identification cells in saline medium was negative, but positive in antiglobulin medium. The patient's serum showed varying reaction intensities with red blood cells treated with different enzymes. MALDI-TOF mass spectrometry and Sanger sequencing revealed a homozygous nonsense variant c.376C>T (p.Gln126Ter) in the ABCG2 gene, resulting in the Jr(a-) phenotype. During family donor selection, the patient's son was found to have a heterozygous variant c.376C>T (p.Gln126Ter), and another heterozygous variant c.421C>A (p.Gln141Lys), which predicted a Jr(a+w) phenotype. Crossmatch tests confirmed the compatibility of blood from the patient's son, which was used to address the urgent blood requirement. Later, rare blood from a Jr(a-) donor from the Guangzhou Blood Center was used for the patient's ongoing treatment, saving the patient's life.</p><p><strong>Conclusion: </strong>Combining classic serological testing with blood group gene typing techniques successfully identified the rare Jr(a-) blood type and high-frequency anti-Jra antibodies. Enzyme-treated red blood cell identification methods confirmed the presence of anti-Jra antibodies. By searching within the family and seeking help from other blood centers, compatible blood was found. This approach may provide insights for resolving similar complex blood matching problems in the future.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 2","pages":"145-150"},"PeriodicalIF":0.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043675","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}

{"title":"[Clinical manifestations and genetic analysis of two patients with familial hypercholesterolemia caused by complex heterozygous variants].","authors":"Xiang Lian, Xiaoyan Li, Kexin Wang, Chunying Tian, Zixi Liu, Xifu Wang","doi":"10.3760/cma.j.cn511374-20241026-00562","DOIUrl":"https://doi.org/10.3760/cma.j.cn511374-20241026-00562","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To investigate the gene detection results of 2 patients with familial hypercholesterolemia (FH) caused by complex heterozygous variation, and to clarify the relationship between clinical manifestations and gene variation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Two patients (patient 1 and 2) with FH who visited Beijing Anzhen Hospital Affiliated to Capital Medical University in 2018 were selected as research subjects. A retrospective study method was used to collect clinical and family history data of the two patients. And 2 mL of peripheral venous blood from each of the two patients was collected, and genomic DNA extraction was performed on the blood samples. Sanger sequencing was used to validate the variant sites of the two patients detected by whole-exome sequencing (WES). Pathogenicity of variants was classified based on the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Classification of Genetic Variants (hereinafter referred to as the \"ACMG Guidelines\"), and the impact of variant was analyzed using multiple bioinformatics tools including SIFT, PolyPhen-2, and SWISS-MODEL. This study has been approved by Beijing Anzhen Hospital Affiliated to Capital Medical University (Ethics No. 2024215X).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Patient 1 initially presented with early-onset coronary heart disease, with initial lipid levels of serum total cholesterol (TC) 9.86 mmol/L (normal reference value: 3.10~5.20 mmol/L) and serum low-density lipoprotein cholesterol (LDL-C) 8.37 mmol/L (normal reference value: 1.27~3.12 mmol/L) on admission. Patient 1 initially underwent treatment with rosuvastatin combined with ezetimibe for one month, but the lipid-lowering effect was not significant. The lipid-lowering therapy was then adjusted to atorvastatin combined with ezetimibe and probucol. After one year of treatment, the patient developed paroxysmal chest pain symptoms. A follow-up lipid profile showed a serum TC level of 4.50 mmol/L and a LDL-C level of 3.55 mmol/L. The lipid-lowering regimen was continued, and the serum LDL-C levels were maintained between 2.65 and 3.66 mmol/L. Patient 2 was found to have an abnormally high blood lipid level and carotid artery hardening during physical examination, with an initial blood lipid level of serum TC 11.82 mmol/L and serum LDL-C 9.63 mmol/L. After receiving rosuvastatain therapy, the lipid-lowering effect was significant. WES revealed that patient 1 carried the heterozygous variants c.1871_1873del(p.Ile624del) and c.1747C&gt;T (p.His583Tyr) in the LDLR gene (NM_000527.4), while patient 2 carried the heterozygous variants c.1747C&gt;T (p.His583Tyr) in the LDLR gene and c.6936_6937inv (p.Ile2313Val) in the APOB gene (NM_000384). According to the ACMG Guidelines, the LDLR gene c.1747C&gt;T (p.His583Tyr) was classified as a pathogenic variant (PS3+PM1+PM2_supporting+PM5+PP2+PP3), and c.1871_1873del (p.Ile624del) was classified as a pathogenic variant (PS3+PS4+PM2_sup","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 2","pages":"212-218"},"PeriodicalIF":0.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144040524","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}

{"title":"[Analysis of clinical feature and genetic variant in a Chinese Han pedigree affected with Darier's disease].","authors":"Shide Zhang, Miao Jiang, Rong Lin, Jiahui Jin, Jingjun Zhao","doi":"10.3760/cma.j.cn511374-20240908-00477","DOIUrl":"10.3760/cma.j.cn511374-20240908-00477","url":null,"abstract":"<p><strong>Objective: </strong>To explore the clinical phenotype and genetic characteristics of a Chinese Han pedigree with Darier's disease (DD).</p><p><strong>Methods: </strong>A DD pedigree, who visited Tongji Hospital of Tongji University on October 22, 2023, was selected as the study subject. Clinical data of the pedigree were collected, and whole exome sequencing was performed on the proband. Suspected variant loci were screened, and Sanger sequencing was used to validate the variant in pedigree members. Bioinformatics analysis was performed on the variant loci. This study was approved by the Medical Ethics Committee of Tongji Hospital of Tongji University Ethics No.K-W-2024-004).</p><p><strong>Results: </strong>The proband is a 67-year-old female with clinical features of DD, such as keratotic papules in sebaceous areas. whole exome sequencing revealed a missense variant, c.68G>A (p.Gly23Glu), in the exon 1 of ATP2A2 gene of the proband. Sanger sequencing showed that the proband's eldest daughter also carried this variant. This variant was not detected in other pedigree members, indicating a co-segregation of the variant with the disease phenotype in the pedigree. According to the interpretation principles of gene variants by the American College of Medical Genetics and Genomics (ACMG), this variant was classified as pathogenic (PS1+PM1+PM2_Supporting+PP1+PP3+PP4).</p><p><strong>Conclusion: </strong>The c.68G>A (p.Gly23Glu) variant in the ATP2A2 gene may be the genetic cause of the disease in this pedigree. This finding further enriches the genetic variant spectrum in DD patients and provides a basis for clinical diagnosis and genetic counseling for patients.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 2","pages":"206-211"},"PeriodicalIF":0.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048957","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}

{"title":"[Research progress of long noncoding RNA in atopic dermatitis].","authors":"Xin Liu, Xinying Cai","doi":"10.3760/cma.j.cn511374-20241024-00554","DOIUrl":"https://doi.org/10.3760/cma.j.cn511374-20241024-00554","url":null,"abstract":"<p><p>Long noncoding RNA (lncRNA) is a type of RNA that is longer than 200 nucleotides and does not encode proteins. Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Genetic susceptibility, damaged skin barrier and immune imbalance play important roles in its pathogenesis. Studies have shown that abnormal expression of lncRNA plays an important role in the development of many human diseases. In recent years, it has been found that various lncRNAs are abnormally expressed in AD patients and are involved in the development of AD. This paper reviews the research progress of lncRNAs in AD, aiming to provide more reference for the pathogenesis and treatment of AD.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 2","pages":"244-248"},"PeriodicalIF":0.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049293","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}

{"title":"[Preliminary analysis of mRNA m7G modifications in human Adenocarcinoma of esophagogastric junction].","authors":"Ziyan Liu, Xiaoyan Wang, Binbin Hu, Shiqi Zhang, Yakun Lang, Yu Fan","doi":"10.3760/cma.j.cn511374-20240724-00408","DOIUrl":"https://doi.org/10.3760/cma.j.cn511374-20240724-00408","url":null,"abstract":"<p><strong>Objective: </strong>To explore the potential role of mRNA m7G modification in the pathogenesis of human adenocarcinoma of esophagogastric junction (AEG).</p><p><strong>Methods: </strong>Pathological tissue specimens from four AEG patients who underwent surgical treatment at the People's Hospital Affiliated to Jiangsu University between 2018 and 2019 were selected. Tumor tissues and adjacent normal tissues were collected from these patients. RNA was extracted from both tissue types and subjected to m7G methylated RNA immunoprecipitation sequencing (m7G-MeRIP-seq) to analyze the patterns of m7G modification, the characteristics of differential m7G modification sites, the differentially expressed mRNA, and the correlation between m7G modification and mRNA expression levels. Differential m7G-modified genes (MSH6, BRCA1, and SOX9) were further validated using methylated RNA immunoprecipitation quantitative PCR (MeRIP-qPCR), while the expression of METTL1 and WDR4 genes was examined by real-time quantitative PCR (RT-qPCR). This study was approved by the Medical Ethics Committee of the People's Hospital Affiliated to Jiangsu University (Ethics No. 20150083).</p><p><strong>Results: </strong>m7G-MeRIP-seq analysis revealed that m7G modifications in both AEG and adjacent normal tissues were predominantly located in the GC-rich region surrounding the internal start codon of mRNA. Differential m7G modification sites between the two groups were closely associated with cancer-related genes. mRNA library analysis showed that differentially expressed mRNA were predominantly upregulated in AEG tissues and downregulated in adjacent normal tissues. Cross-analysis indicated that genes with hypermethylation tended to exhibit upregulated expression, while genes with hypomethylation were typically downregulated in AEG tissues. MeRIP-qPCR validation confirmed that the mRNA expression of MSH6, BRCA1, and SOX9 were significantly upregulated in AEG tissues compared to adjacent normal tissues (AEG vs. normal, P < 0.05). RT-qPCR results demonstrated that the mRNA expression levels of METTL1 and WDR4 were also upregulated in AEG tissues (AEG vs. normal, P < 0.000 5).</p><p><strong>Conclusion: </strong>These findings suggest that mRNA m7G modification plays a significant role in the development of AEG. Furthermore, proteins as METTL1 and WDR4 may facilitate AEG progression by regulating mRNA m7G modification. These results provide valuable insights into the molecular mechanisms underlying AEG and may inform future therapeutic strategies for this malignancy.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 2","pages":"187-197"},"PeriodicalIF":0.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048960","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}

{"title":"[Identification of a case with novel HLA-DRB1*12:106 allele].","authors":"Li'na Dong, Nanying Chen, Yizhen He, Wei Zhang, Faming Zhu","doi":"10.3760/cma.j.cn511374-20240627-00355","DOIUrl":"https://doi.org/10.3760/cma.j.cn511374-20240627-00355","url":null,"abstract":"<p><strong>Objective: </strong>To identify the nucleotide sequence of a novel HLA-DRB1*12:106 allele.</p><p><strong>Methods: </strong>A blood donor who was joined into the database for platelet matching transfusion at the Blood Center of Zhejiang Province in 2023 was selected as the study subject. HLA genotyping was carried out through next-generation sequencing based on AllType NGS 11 locus, AllType FASTPlex NGS reagents, and Sanger sequencing method. The HLA genotype of the donor by Sanger sequencing and next generation sequencing were assigned by using uTYPE 7.3 and TypeStream Visual 3.0 software, respectively. This study was approved by Medical Ethics Committee of the Zhejiang Blood Center (Ethics No. Provincial Blood Center Ethics Review 2022 Research No. 001).</p><p><strong>Results: </strong>A novel HLA-DRB1*12 allele has been identified, and the full coding sequence has been submitted to the GenBank database (No. OR101190), and the length of submitted sequence was 801 bp, which was officially named as HLA-DRB1*12:106 by the WHO Nomenclature Committee for Factors of the HLA System (submission No. HWS10066755). Compared with the sequence of the highest homology (HLA-DRB1*12:01:01:01 allele), a single nucleotide change was identified at position 344 T>G in the exon 2 of the HLA-DRB1*12:106, which has resulted in replacement of Valine by Glycine at residue 86. The HLA genotype of the proband was determined as HLA-A*02:01, 11:01;-B*13:02, 40:01;-C*01:02, 03:03;-DRB1*07:01, 12:106;-DRB3*01:01;-DRB4*01:03;-DQA1*02:01,04:01;-DQB1*02:02,04:02;-DPA1*01:03,01:03; -- DPB1*02:01:02G,04:01:01G.</p><p><strong>Conclusion: </strong>A novel HLA-DRB1 allele has been identified in the Chinese population. The mutated amino acid, located in the peptide binding region of the β chain, may affect the binding characteristics of antigen peptides.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 2","pages":"151-155"},"PeriodicalIF":0.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043635","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}

{"title":"[Mechanism of BNIP3-mediated mitophagy in m.3635G>A related Leber hereditary optic neuropathy].","authors":"Zhen Liu, Wei Guan, Juanjuan Zhang, Minxin Guan","doi":"10.3760/cma.j.cn511374-20221101-00574","DOIUrl":"https://doi.org/10.3760/cma.j.cn511374-20221101-00574","url":null,"abstract":"<p><strong>Objective: </strong>To explore the mechanism of BNIP3-mediated mitophagy in m.3635G>A related Leber's hereditary optic neuropathy (LHON).</p><p><strong>Methods: </strong>A trans-mitochondrial cybrid cell line derived from a Chinese LHON patient carrying the m.3635G>A, diagnosed at the Eye Hospital of Wenzhou Medical University in September 2013, was selected as the study subject. A trans-mitochondrial cybrid cell line from a healthy control with an identical mitochondrial background was included as a control. Immunofluorescence, real-time quantitative PCR (RT-qPCR), and Western blotting were employed to assess the expression of autophagy-related proteins, aiming to explore the role of BNIP3-mediated mitophagy in m.3635G>A related LHON. This study was approved by the Medical Ethics Committee of the Eye Hospital of Wenzhou Medical University (Ethics No. 2023-J-096).</p><p><strong>Results: </strong>Compared with the control group, the protein expression levels of autophagy-related markers LC3 (LC3-II/LC3-I) and LAMP1 were significantly reduced in the variant group (P < 0.05). Additionally, the protein levels of macroautophagy-related proteins ATG12, ATG7, and ATG5 were also significantly decreased (P < 0.05). Compared with the control cells, the mRNA and protein expression levels of mitophagy-associated protein BNIP3 were significantly reduced in the cells of the variant group (P < 0.05). Compared with the control group, both mRNA and protein expression levels of the mitophagy-related protein BNIP3 were significantly reduced in the variant group (P < 0.05).</p><p><strong>Conclusion: </strong>The m.3635G>A inhibits BNIP3-mediated mitophagy, thereby contributing to the pathogenesis of LHON.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 2","pages":"198-205"},"PeriodicalIF":0.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990120","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}