首页 > 最新文献

中华医学遗传学杂志最新文献

英文 中文
[Genetic analysis of an individual with A3 phenotype due to variant of A-glycosyltransferase enzyme gene]. [A-糖基转移酶基因变异导致 A3 表型个体的遗传分析]。
Q4 Medicine Pub Date : 2024-07-10 DOI: 10.3760/cma.j.cn511374-20230414-00211
Minxi Li, Xu Zhang, Hua Fan

Objective: To explore the serological characteristics and molecular mechanism underlying an individual with A3 phenotype.

Methods: A 27-year-old ethnic Han Chinese woman presented at the Fourth Affiliated Hospital of China Medical University on May 12, 2022 was selected as the study subject. ABO blood type was determined with standard serological techniques. The ABO gene was subjected to direct sequencing of PCR products. Exons 6 and 7 of the ABO gene were sequenced using specific primers to determine the haplotypes. Bioinformatic software was used to analyze the structure of the mutant protein.

Results: Serological typing of the ABO blood group has suggested a rare A3 phenotype. The proband was found to harbor heterozygous c.261delG, c.467C>T and c.745C>T variants by direct sequencing. Single strand sequencing revealed that she has harbored ABO*A3.07 and ABO*O.01.01 alleles. The ABO*A3.07 allele has contained a c.745C>T (p.R249W) variant on the background of an ABO*A1.02 allele. The p.R249W substitution was predicted to be probably damaging by the PolyPhen2 software. The free energy change (ΔΔG) value predicted it to have a destabilizing effect on the GTA protein. Meanwhile, modeling of the 3D structure has predicted that the p.R249W amino acid substitution may alter the hydrogen bond network of the GTA protein.

Conclusion: The p.R249W substitution of the α-1,3-N-acetylgalactosaminyltransferase gene may reduce the antigen expression owing to a great destabilizing effect on the structure and function of the GTA protein.

目的:探讨 A3 表型个体的血清学特征和分子机制:探讨 A3 表型个体的血清学特征和分子机制:选取 2022 年 5 月 12 日在中国医科大学附属第四医院就诊的一名 27 岁汉族女性作为研究对象。采用标准血清学技术测定 ABO 血型。对 ABO 基因的 PCR 产物进行了直接测序。使用特定引物对 ABO 基因的第 6 和第 7 外显子进行测序,以确定单倍型。使用生物信息软件分析突变蛋白的结构:ABO血型的血清学分型显示出罕见的A3表型。通过直接测序,发现该患者携带杂合c.261delG、c.467C>T和c.745C>T变异。单链测序显示她携带 ABO*A3.07 和 ABO*O.01.01 等位基因。在 ABO*A1.02 等位基因的背景上,ABO*A3.07 等位基因含有 c.745C>T(p.R249W)变异。根据 PolyPhen2 软件的预测,p.R249W 突变可能具有破坏性。自由能变化(ΔΔG)值预测它对 GTA 蛋白有破坏稳定的作用。同时,三维结构模型预测 p.R249W 氨基酸取代可能会改变 GTA 蛋白的氢键网络:结论:α-1,3-N-乙酰半乳糖氨基转移酶基因的 p.R249W 取代可能会降低抗原的表达量,因为它对 GTA 蛋白的结构和功能有很大的不稳定作用。
{"title":"[Genetic analysis of an individual with A3 phenotype due to variant of A-glycosyltransferase enzyme gene].","authors":"Minxi Li, Xu Zhang, Hua Fan","doi":"10.3760/cma.j.cn511374-20230414-00211","DOIUrl":"10.3760/cma.j.cn511374-20230414-00211","url":null,"abstract":"<p><strong>Objective: </strong>To explore the serological characteristics and molecular mechanism underlying an individual with A3 phenotype.</p><p><strong>Methods: </strong>A 27-year-old ethnic Han Chinese woman presented at the Fourth Affiliated Hospital of China Medical University on May 12, 2022 was selected as the study subject. ABO blood type was determined with standard serological techniques. The ABO gene was subjected to direct sequencing of PCR products. Exons 6 and 7 of the ABO gene were sequenced using specific primers to determine the haplotypes. Bioinformatic software was used to analyze the structure of the mutant protein.</p><p><strong>Results: </strong>Serological typing of the ABO blood group has suggested a rare A3 phenotype. The proband was found to harbor heterozygous c.261delG, c.467C>T and c.745C>T variants by direct sequencing. Single strand sequencing revealed that she has harbored ABO*A3.07 and ABO*O.01.01 alleles. The ABO*A3.07 allele has contained a c.745C>T (p.R249W) variant on the background of an ABO*A1.02 allele. The p.R249W substitution was predicted to be probably damaging by the PolyPhen2 software. The free energy change (ΔΔG) value predicted it to have a destabilizing effect on the GTA protein. Meanwhile, modeling of the 3D structure has predicted that the p.R249W amino acid substitution may alter the hydrogen bond network of the GTA protein.</p><p><strong>Conclusion: </strong>The p.R249W substitution of the α-1,3-N-acetylgalactosaminyltransferase gene may reduce the antigen expression owing to a great destabilizing effect on the structure and function of the GTA protein.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 7","pages":"862-865"},"PeriodicalIF":0.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471370","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
[Genetic study of a rare Chinese pedigree with a recombination occurring between the HLA-A/C loci in both parents]. [父母双方 HLA-A/C 基因座之间发生重组的罕见中国血统遗传学研究]。
Q4 Medicine Pub Date : 2024-07-10 DOI: 10.3760/cma.j.cn511374-20230505-00260
Tianju Wang, Manni Wang, Jun Qi, Yuhui Li, Junhua Wu, Lixia Shang, Le Chen

Objective: To analyze a Chinese pedigree with a recombination occurring between the HLA-A/C loci in both parents.

Methods: A patient who was planning to undergo hematopoietic stem cell transplantation due to "aplastic anemia" in February 2022 was selected as the study subject. Peripheral blood samples were collected from the patient, his parents and brother. HLA-A/C/B/DRB1/DQB1 high-resolution typing was carried out by using sequence-based typing and sequence-specific oligonucleotides. The recombination was identified by pedigree analysis. The HLA haplotype of each individual was identified by genealogical analysis. The parentage possibility was determined by short tandem repeat analysis. HLA-A/C/B/DRB1/DRB345/DQA1/DQB1/DPA1/DPB1 were determined with next-generation high-throughput sequence-based typing. The recombination sites were analyzed by family study.

Results: The high parentage possibilities of the family was confirmed by short tandem repeat analysis. Recombination was found between the HLA-A*24:02 A*33:03/C*14:03 in the paternally transmitted haplotype, whilst HLA-A*01:01 A*03:01/C*08:02 was found in the maternally transmitted haplotype, which had resulted in two novel HLA haplotypes in the proband.

Conclusion: A rare case with simultaneous recombination of the paternal and maternal HLA-A/C loci has been discovered, which may facilitate further study of the mechanisms of the HLA recombination.

目的分析一个父母双方 HLA-A/C 基因座之间发生重组的中国血统:选取一名因 "再生障碍性贫血 "而计划于 2022 年 2 月接受造血干细胞移植的患者作为研究对象。采集了患者及其父母和兄弟的外周血样本。使用基于序列的分型和序列特异性寡核苷酸进行了 HLA-A/C/B/DRB1/DQB1 高分辨率分型。通过血统分析确定了重组。通过系谱分析确定了每个个体的 HLA 单倍型。通过短串联重复分析确定亲子关系的可能性。HLA-A/C/B/DRB1/DRB345/DQA1/DQB1/DPA1/DPB1通过下一代高通量序列分型确定。通过家族研究分析了重组位点:结果:短串联重复分析证实了该家族的高亲缘可能性。结果:通过短串联重复分析确认了该家族的高亲缘可能性。在父方传播的单倍型中发现了 HLA-A*24:02 A*33:03/C*14:03 之间的重组,而在母方传播的单倍型中发现了 HLA-A*01:01 A*03:01/C*08:02 ,这导致了该患者体内出现了两种新的 HLA 单倍型:结论:这是一个罕见的父系和母系HLA-A/C位点同时重组的病例,有助于进一步研究HLA重组的机制。
{"title":"[Genetic study of a rare Chinese pedigree with a recombination occurring between the HLA-A/C loci in both parents].","authors":"Tianju Wang, Manni Wang, Jun Qi, Yuhui Li, Junhua Wu, Lixia Shang, Le Chen","doi":"10.3760/cma.j.cn511374-20230505-00260","DOIUrl":"10.3760/cma.j.cn511374-20230505-00260","url":null,"abstract":"<p><strong>Objective: </strong>To analyze a Chinese pedigree with a recombination occurring between the HLA-A/C loci in both parents.</p><p><strong>Methods: </strong>A patient who was planning to undergo hematopoietic stem cell transplantation due to \"aplastic anemia\" in February 2022 was selected as the study subject. Peripheral blood samples were collected from the patient, his parents and brother. HLA-A/C/B/DRB1/DQB1 high-resolution typing was carried out by using sequence-based typing and sequence-specific oligonucleotides. The recombination was identified by pedigree analysis. The HLA haplotype of each individual was identified by genealogical analysis. The parentage possibility was determined by short tandem repeat analysis. HLA-A/C/B/DRB1/DRB345/DQA1/DQB1/DPA1/DPB1 were determined with next-generation high-throughput sequence-based typing. The recombination sites were analyzed by family study.</p><p><strong>Results: </strong>The high parentage possibilities of the family was confirmed by short tandem repeat analysis. Recombination was found between the HLA-A*24:02 A*33:03/C*14:03 in the paternally transmitted haplotype, whilst HLA-A*01:01 A*03:01/C*08:02 was found in the maternally transmitted haplotype, which had resulted in two novel HLA haplotypes in the proband.</p><p><strong>Conclusion: </strong>A rare case with simultaneous recombination of the paternal and maternal HLA-A/C loci has been discovered, which may facilitate further study of the mechanisms of the HLA recombination.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 7","pages":"853-857"},"PeriodicalIF":0.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471371","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
[Clinical characteristics and genetic analysis of two children with X-linked Centronuclear myopathy due to variants of MTM1 gene]. [两名因 MTM1 基因变异而患有 X 连锁中心核肌病的儿童的临床特征和遗传分析]。
Q4 Medicine Pub Date : 2024-07-10 DOI: 10.3760/cma.j.cn511374-20230606-00345
Jin Wang, Dan Wang, Tingting Li, Lingkong Zeng, Shi Wang

Objective: To explore the clinical and genetic characteristics of two newborns with Central nuclear myopathy (CNM).

Methods: Two newborns with CNM diagnosed clinically at Wuhan Children's Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology in April 2019 and November 2021 were selected as the study subjects, and their clinical data was collected. Both newborns and their parents were subjected chromosomal karyotyping analysis and whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing. Pathogenicity of the candidate variants was evaluated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG).

Results: Patient 1 was a male neonate and Patient 2 was a 20-day-old male infant. Both newborns had featured difficulty in breathing and swallowing. WES revealed that both had harbored hemizygous variants of the MTM1 gene, which were verified by Sanger sequencing. Patient 1 had harbored a c.1261A>G variant. Based on the ACMG guidelines, it was rated as pathogenic (PVS1+PM2_Supporting+PP3). Patient 2 harbored a c.342delT variant, which was also rated as pathogenic (PVS1+PM2_Supporting+PP3).

Conclusion: The c.1261A>G and c.342delT variants of the MTM1 gene probably underlay the pathogenesis of CNM in the two patients.

目的:探讨两名患有中央核肌病(CNM)的新生儿的临床和遗传特征:探讨两名新生儿中央核肌病(CNM)的临床和遗传特征:选取2019年4月和2021年11月在华中科技大学同济医学院附属武汉儿童医院临床确诊为中央核肌病的两名新生儿作为研究对象,收集其临床资料。新生儿及其父母均接受了染色体核型分析和全外显子组测序(WES)。通过桑格测序验证了候选变异。根据美国医学遗传学和基因组学学院(ACMG)的指南对候选变异的致病性进行了评估:患者 1 是一名男性新生儿,患者 2 是一名出生 20 天的男婴。两个新生儿都有呼吸和吞咽困难的特征。WES 发现两人都携带 MTM1 基因的半杂合子变异,并通过桑格测序进行了验证。患者1携带c.1261A>G变异。根据 ACMG 指南,该变异被评为致病性变异(PVS1+PM2_Supporting+PP3)。患者 2 携带的 c.342delT 变异也被评为致病性(PVS1+PM2_支持+PP3):结论:MTM1 基因的 c.1261A>G 和 c.342delT 变体可能是这两名患者 CNM 的发病机制。
{"title":"[Clinical characteristics and genetic analysis of two children with X-linked Centronuclear myopathy due to variants of MTM1 gene].","authors":"Jin Wang, Dan Wang, Tingting Li, Lingkong Zeng, Shi Wang","doi":"10.3760/cma.j.cn511374-20230606-00345","DOIUrl":"10.3760/cma.j.cn511374-20230606-00345","url":null,"abstract":"<p><strong>Objective: </strong>To explore the clinical and genetic characteristics of two newborns with Central nuclear myopathy (CNM).</p><p><strong>Methods: </strong>Two newborns with CNM diagnosed clinically at Wuhan Children's Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology in April 2019 and November 2021 were selected as the study subjects, and their clinical data was collected. Both newborns and their parents were subjected chromosomal karyotyping analysis and whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing. Pathogenicity of the candidate variants was evaluated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG).</p><p><strong>Results: </strong>Patient 1 was a male neonate and Patient 2 was a 20-day-old male infant. Both newborns had featured difficulty in breathing and swallowing. WES revealed that both had harbored hemizygous variants of the MTM1 gene, which were verified by Sanger sequencing. Patient 1 had harbored a c.1261A>G variant. Based on the ACMG guidelines, it was rated as pathogenic (PVS1+PM2_Supporting+PP3). Patient 2 harbored a c.342delT variant, which was also rated as pathogenic (PVS1+PM2_Supporting+PP3).</p><p><strong>Conclusion: </strong>The c.1261A>G and c.342delT variants of the MTM1 gene probably underlay the pathogenesis of CNM in the two patients.</p>","PeriodicalId":39319,"journal":{"name":"Chinese Journal of Medical Genetics","volume":"41 7","pages":"812-816"},"PeriodicalIF":0.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471364","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 clinical features and genetic variants in three children with late-onset Multiple acyl-Coenzyme A dehydrogenase deficiency]. [分析三名晚发型多酰基辅酶 A 脱氢酶缺乏症患儿的临床特征和遗传变异]。
Q4 Medicine Pub Date : 2024-07-10 DOI: 10.3760/cma.j.cn511374-20230611-00355
Mengqin Wang, Xi Wang, Ang Ma, Yu Gu, Xiaotong Zhao, Yaodong Zhang, Dongxiao Li, Yongxing Chen, Haiyan Wei

Objective: To explore the clinical characteristics and genetic variants in three children with late-onset Multiple acyl-Coenzyme A dehydrogenase deficiency (MADD type Ⅲ).

Methods: Clinical data of three children diagnosed with late-onset MADD at the Children's Hospital Affiliated to Zhengzhou University between March 2020 and March 2022 were retrospectively analyzed. All children were subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing. All children had received improved metabolic therapy and followed up for 1 ~ 3 years.

Results: The children had included 2 males and 1 female, and aged from 2 months to 11 years and 7 months. Child 1 had intermittent vomiting, child 2 had weakness in lower limbs, while child 3 had no symptom except abnormal neonatal screening. Tandem mass spectrometry of the three children showed elevation of multiple acylcarnitines with short, medium and long chains. Children 1 and 2 showed increased glutaric acid and multiple dicarboxylic acids by urine Gas chromatography-mass spectrometry (GC-MS) analysis. All children were found to harbor compound heterozygous variants of the ETFDH gene, including a paternal c.1211T>C (p.M404T) and a maternal c.488-22T>G variant in child 1, a paternal c.1717C>T (p.Q573X) and a maternal c.250G>A (p.A84T) variant in child 2, and a paternal c.1285+1G>A and maternal c.629A>G (p.S210N) variant in child 3. As for the treatment, high-dose vitamin B2, levocarnitine and coenzyme Q10 were given to improve the metabolism, in addition with a low fat, hypoproteinic and high carbohydrate diet. All children showed a stable condition with normal growth and development during the follow-up.

Conclusion: The compound heterozygous variants of the ETFDH gene probably underlay the muscle weakness, remittent vomiting, elevated short, medium, and long chain acylcarnitine, as well as elevated glutaric acid and various dicarboxylic acids in the three children with type Ⅲ MADD.

目的探讨3例晚期多酰基辅酶A脱氢酶缺乏症(MADDⅢ型)患儿的临床特征和遗传变异:方法:回顾性分析2020年3月至2022年3月期间在郑州大学附属儿童医院确诊的3名晚期MADD患儿的临床资料。所有患儿均接受了全外显子组测序(WES),并通过桑格测序验证了候选变异。所有患儿均接受了改善代谢治疗,并随访了1至3年:患儿中2男1女,年龄从2个月到11岁零7个月不等。1 号患儿有间歇性呕吐,2 号患儿下肢无力,3 号患儿除新生儿筛查异常外无其他症状。对三个孩子进行的串联质谱分析表明,短链、中链和长链的多种酰基肉碱含量升高。尿液气相色谱-质谱(GC-MS)分析显示,1 号和 2 号患儿的戊二酸和多种二羧酸含量增加。研究发现,所有患儿的 ETFDH 基因都存在复合杂合变异,其中 1 号患儿的父基因 c.1211T>C (p.M404T) 和母基因 c.488-22T>G变异;患儿 2 的父基因 c.1717C>T (p.Q573X) 和母基因 c.250G>A (p.A84T) 变异;患儿 3 的父基因 c.1285+1G>A 和母基因 c.629A>G (p.S210N) 变异。在治疗方面,除了低脂肪、低蛋白和高碳水化合物饮食外,还给予大剂量维生素 B2、左旋肉碱和辅酶 Q10 以改善新陈代谢。所有患儿在随访期间病情稳定,生长发育正常:结论:ETFDH基因的复合杂合子变异可能是三名Ⅲ型MADD患儿出现肌无力、再发性呕吐、短链、中链和长链酰基肉碱升高以及戊二酸和各种二羧酸升高的主要原因。
{"title":"[Analysis of clinical features and genetic variants in three children with late-onset Multiple acyl-Coenzyme A dehydrogenase deficiency].","authors":"Mengqin Wang, Xi Wang, Ang Ma, Yu Gu, Xiaotong Zhao, Yaodong Zhang, Dongxiao Li, Yongxing Chen, Haiyan Wei","doi":"10.3760/cma.j.cn511374-20230611-00355","DOIUrl":"10.3760/cma.j.cn511374-20230611-00355","url":null,"abstract":"<p><strong>Objective: </strong>To explore the clinical characteristics and genetic variants in three children with late-onset Multiple acyl-Coenzyme A dehydrogenase deficiency (MADD type Ⅲ).</p><p><strong>Methods: </strong>Clinical data of three children diagnosed with late-onset MADD at the Children's Hospital Affiliated to Zhengzhou University between March 2020 and March 2022 were retrospectively analyzed. All children were subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing. All children had received improved metabolic therapy and followed up for 1 ~ 3 years.</p><p><strong>Results: </strong>The children had included 2 males and 1 female, and aged from 2 months to 11 years and 7 months. Child 1 had intermittent vomiting, child 2 had weakness in lower limbs, while child 3 had no symptom except abnormal neonatal screening. Tandem mass spectrometry of the three children showed elevation of multiple acylcarnitines with short, medium and long chains. Children 1 and 2 showed increased glutaric acid and multiple dicarboxylic acids by urine Gas chromatography-mass spectrometry (GC-MS) analysis. All children were found to harbor compound heterozygous variants of the ETFDH gene, including a paternal c.1211T>C (p.M404T) and a maternal c.488-22T>G variant in child 1, a paternal c.1717C>T (p.Q573X) and a maternal c.250G>A (p.A84T) variant in child 2, and a paternal c.1285+1G>A and maternal c.629A>G (p.S210N) variant in child 3. As for the treatment, high-dose vitamin B<sub>2</sub>, levocarnitine and coenzyme Q10 were given to improve the metabolism, in addition with a low fat, hypoproteinic and high carbohydrate diet. All children showed a stable condition with normal growth and development during the follow-up.</p><p><strong>Conclusion: </strong>The compound heterozygous variants of the ETFDH gene probably underlay the muscle weakness, remittent vomiting, elevated short, medium, and long chain acylcarnitine, as well as elevated glutaric acid and various dicarboxylic acids in the three children with type Ⅲ MADD.</p>","PeriodicalId":39319,"journal":{"name":"Chinese Journal of Medical Genetics","volume":"41 7","pages":"790-796"},"PeriodicalIF":0.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471356","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
[Identification of novel genetic loci associated with major depressive disorder and the hippocampus in a European population using the condFDR method]. [使用 condFDR 方法鉴定欧洲人群中与重度抑郁障碍和海马相关的新基因位点]。
Q4 Medicine Pub Date : 2024-07-10 DOI: 10.3760/cma.j.cn511374-20230515-00285
Qing Du, Minglan Yu, Xuemei Liang, Tingting Wang, Rongfang He, Wei Lei, Jing Chen, Chaohua Huang, Kezhi Liu, Bo Xiang

Objective: To identify additional loci associated with depression and the hippocampus (HIP) through genome-wide association study.

Methods: The depression-related genome-wide association study (GWAS) meta summary data was downloaded from the official website of the Psychiatric Genomics Consortium, which had involved 170 756 cases and 329 443 controls. The left and right hippocampal volume GWAS data sets were downloaded from the UK Biobank, which involved 33 224 participants. The conditional false discovery rate (condFDR) was used to identify novel genetic loci for depression and left and right hippocampal volumes, and a conjunctional false discovery rate (conjFDR) was used to evaluate the enrichment of pleiotropic loci between depression and left and right hippocampal volumes.

Results: Respectively, 7, 13, and 12 new loci have been associated with depression, left hippocampal volume and right hippocampal volume, with a significant threshold of condFDR < 0.01. A site of rs1267073 locus was found to be shared by the depression and right hippocampal volume with a threshold of conjFDR < 0.01.

Conclusion: Above findings have provided more insights into the genetic mechanisms underlying the volume of hippocampus and the risk for depression. The results may also provide evidence for future clinical trials for treating depression.

目的:通过全基因组关联研究确定与抑郁症和海马(HIP)相关的其他基因位点:通过全基因组关联研究,确定更多与抑郁症和海马(HIP)相关的基因位点:抑郁症相关的全基因组关联研究(GWAS)元摘要数据从精神病基因组学联盟的官方网站下载,涉及 170 756 例病例和 329 443 例对照。左侧和右侧海马体积 GWAS 数据集从英国生物库下载,涉及 33 224 名参与者。利用条件错误发现率(condFDR)来确定抑郁症和左右海马体积的新遗传位点,利用联合错误发现率(conjunctional false discovery rate,conjFDR)来评估抑郁症和左右海马体积之间多向性位点的富集情况:结果:分别有7个、13个和12个新位点与抑郁、左侧海马体积和右侧海马体积相关,显著阈值为condFDR<0.01。其中,rs1267073位点与抑郁症和右侧海马体积共享,conjFDR<0.01:上述发现为海马体积和抑郁风险的遗传机制提供了更多的见解。这些结果也可为未来治疗抑郁症的临床试验提供证据。
{"title":"[Identification of novel genetic loci associated with major depressive disorder and the hippocampus in a European population using the condFDR method].","authors":"Qing Du, Minglan Yu, Xuemei Liang, Tingting Wang, Rongfang He, Wei Lei, Jing Chen, Chaohua Huang, Kezhi Liu, Bo Xiang","doi":"10.3760/cma.j.cn511374-20230515-00285","DOIUrl":"10.3760/cma.j.cn511374-20230515-00285","url":null,"abstract":"<p><strong>Objective: </strong>To identify additional loci associated with depression and the hippocampus (HIP) through genome-wide association study.</p><p><strong>Methods: </strong>The depression-related genome-wide association study (GWAS) meta summary data was downloaded from the official website of the Psychiatric Genomics Consortium, which had involved 170 756 cases and 329 443 controls. The left and right hippocampal volume GWAS data sets were downloaded from the UK Biobank, which involved 33 224 participants. The conditional false discovery rate (condFDR) was used to identify novel genetic loci for depression and left and right hippocampal volumes, and a conjunctional false discovery rate (conjFDR) was used to evaluate the enrichment of pleiotropic loci between depression and left and right hippocampal volumes.</p><p><strong>Results: </strong>Respectively, 7, 13, and 12 new loci have been associated with depression, left hippocampal volume and right hippocampal volume, with a significant threshold of condFDR < 0.01. A site of rs1267073 locus was found to be shared by the depression and right hippocampal volume with a threshold of conjFDR < 0.01.</p><p><strong>Conclusion: </strong>Above findings have provided more insights into the genetic mechanisms underlying the volume of hippocampus and the risk for depression. The results may also provide evidence for future clinical trials for treating depression.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 7","pages":"769-775"},"PeriodicalIF":0.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471373","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 clinical features of 193 Chinese patients with McCune-Albright syndrome through a literature review]. [通过文献综述分析 193 名中国麦库恩-阿尔布莱特综合征患者的临床特征]。
Q4 Medicine Pub Date : 2024-07-10 DOI: 10.3760/cma.j.cn511374-20230425-00242
Xin Feng, Ke Yuan, Huifei Lu, Haifeng Tu, Jianfang Zhu, Yanlan Fang, Qingfeng Yan, Chunlin Wang

Objective: To retrospectively analyze the clinical characteristics of 193 Chinese patients with McCune-Albright syndrome (MAS).

Methods: By using keywords "McCune-Albright syndrome", "Albright syndrome", or " fibrous dysplasia " as the search terms, 193 cases of MAS reported in China from January 1990 to November 2022 from the Wanfang data, CNKI, VIP, PubMed, and Embase databases were obtained, and their clinical data was retrospectively analyzed. Intergroup comparisons were carried out by using t test, Mann-Whitney U test, and X2 test.

Results: The 193 MAS patients had included 42 males and 151 females, with the median first-visit age of females being younger than males. The typical triad group had accounted for 46.1% of patients, and the middle first-visit and diagnosis age was younger than the atypical group. The primary reason for first-visit in males of MAS was fibrous dysplasia (FD), whilst that in females of MAS was peripheral precocious puberty (PPP). FD has occurred in 84.5% of the patients, with an average age of onset age being 6.1 years old, and 90% was ≤ 16 years of age. Endocrine hyperfunction was found in 79.3% of the patients, with a higher proportion in females compared with males (P < 0.05). Pituitary involvement was seen in 21.8% of the patients, and the incidence of craniofacial FD and cranial nerve compression was significantly higher in those with elevated growth hormone (GH) than without (P < 0.05). Café-au-Lait Spots were noted in 86.5% of the patients, and 28.3% (28/99) had located on the different side of FD.

Conclusion: Most MAS patients had atypical manifestations and multi-systemic involvement. It is more common and occurs earlier in females. The most common reasons for initial diagnosis in male and female patients were FD and PPP, respectively. Patients with elevated GH should be examined for cranial nerve compression.

目的:回顾性分析193例中国麦库恩-阿尔布莱特综合征患者的临床特征:回顾性分析193例中国麦库恩-阿尔布莱特综合征(MAS)患者的临床特征:方法:以 "McCune-Albright综合征"、"Albright综合征 "或 "纤维发育不良 "为关键词,从万方数据、CNKI、VIP、PubMed和Embase数据库中获取1990年1月至2022年11月中国报道的193例MAS患者,并对其临床资料进行回顾性分析。组间比较采用t检验、Mann-Whitney U检验和X2检验:193例MAS患者中,男性42例,女性151例,女性首次就诊年龄的中位数小于男性。典型三联征组占 46.1%,首次就诊年龄和诊断年龄的中位数均小于非典型组。MAS男性患者首次就诊的主要原因是纤维发育不良(FD),而MAS女性患者首次就诊的主要原因是外周性早熟(PPP)。84.5%的患者出现纤维发育不良,平均发病年龄为6.1岁,90%的患者年龄小于16岁。79.3%的患者出现内分泌功能亢进,女性比例高于男性(P < 0.05)。21.8%的患者脑垂体受累,生长激素(GH)升高的患者颅面FD和颅神经受压的发生率明显高于未受累者(P<0.05)。86.5%的患者有咖啡斑,28.3%(28/99)的咖啡斑位于FD的另一侧:结论:大多数MAS患者表现不典型,多系统受累。结论:大多数 MAS 患者表现不典型,并有多系统受累,女性更常见,发病更早。男性和女性患者最初确诊的最常见原因分别是 FD 和 PPP。GH升高的患者应检查是否有颅神经受压。
{"title":"[Analysis of clinical features of 193 Chinese patients with McCune-Albright syndrome through a literature review].","authors":"Xin Feng, Ke Yuan, Huifei Lu, Haifeng Tu, Jianfang Zhu, Yanlan Fang, Qingfeng Yan, Chunlin Wang","doi":"10.3760/cma.j.cn511374-20230425-00242","DOIUrl":"10.3760/cma.j.cn511374-20230425-00242","url":null,"abstract":"<p><strong>Objective: </strong>To retrospectively analyze the clinical characteristics of 193 Chinese patients with McCune-Albright syndrome (MAS).</p><p><strong>Methods: </strong>By using keywords \"McCune-Albright syndrome\", \"Albright syndrome\", or \" fibrous dysplasia \" as the search terms, 193 cases of MAS reported in China from January 1990 to November 2022 from the Wanfang data, CNKI, VIP, PubMed, and Embase databases were obtained, and their clinical data was retrospectively analyzed. Intergroup comparisons were carried out by using t test, Mann-Whitney U test, and X<sup>2</sup> test.</p><p><strong>Results: </strong>The 193 MAS patients had included 42 males and 151 females, with the median first-visit age of females being younger than males. The typical triad group had accounted for 46.1% of patients, and the middle first-visit and diagnosis age was younger than the atypical group. The primary reason for first-visit in males of MAS was fibrous dysplasia (FD), whilst that in females of MAS was peripheral precocious puberty (PPP). FD has occurred in 84.5% of the patients, with an average age of onset age being 6.1 years old, and 90% was ≤ 16 years of age. Endocrine hyperfunction was found in 79.3% of the patients, with a higher proportion in females compared with males (P < 0.05). Pituitary involvement was seen in 21.8% of the patients, and the incidence of craniofacial FD and cranial nerve compression was significantly higher in those with elevated growth hormone (GH) than without (P < 0.05). Café-au-Lait Spots were noted in 86.5% of the patients, and 28.3% (28/99) had located on the different side of FD.</p><p><strong>Conclusion: </strong>Most MAS patients had atypical manifestations and multi-systemic involvement. It is more common and occurs earlier in females. The most common reasons for initial diagnosis in male and female patients were FD and PPP, respectively. Patients with elevated GH should be examined for cranial nerve compression.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 7","pages":"776-782"},"PeriodicalIF":0.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471357","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
[Clinical characteristics and genetic analysis of a child with Neutral lipid storage disease with myopathy]. [中性脂质贮积症伴肌病患儿的临床特征和基因分析]。
Q4 Medicine Pub Date : 2024-07-10 DOI: 10.3760/cma.j.cn511374-20220523-00312
Yu Zhang, Fenglei Guo, Nadan Lu, Miaomiao Tang, Dao Wang

Objective: To explore the clinical phenotype and genetic basis of a child with Neutral lipid storage disease with myopathy (NLSDM).

Methods: A child who was admitted to the First Affiliated Hospital of Zhengzhou University in February 2021 for a history of elevated creatine kinase (CK) for over 2 months was selected as the study subject. Clinical and laboratory examinations were carried out, and the child was subjected to whole exome sequencing. Candidate variants were validated by Sanger sequencing of her family members.

Results: The patient, a 9-year-old female, had exhibited weakness in the lower limbs, elevated CK level, and refractory cardiomyotrophy. Genetic testing revealed that she has harbored c.32C>G (p.S11W) and c.516C>G (p.N172K) compound heterozygous variants of the PNPLA2 gene, which were respectively inherited from her mother and father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as likely pathogenic (PM1+PM2_Supporting+PP3+PP4).

Conclusion: The c.32C>G (p.S11W) and c.516C>G (p.N172K) compound heterozygous variants of the PNPLA2 gene probably underlay the myasthenia gravis and elevated creatine kinase in this child.

目的:探讨中性脂肪贮积症伴肌病患儿的临床表型和遗传基础:探讨中性脂质贮积症伴肌病(NLSDM)患儿的临床表型和遗传基础:方法:选取2021年2月因肌酸激酶(CK)升高2个多月而入住郑州大学第一附属医院的一名患儿作为研究对象。研究人员对该患儿进行了临床和实验室检查,并对其进行了全外显子组测序。其家庭成员的桑格测序验证了候选变异:患者为一名 9 岁女性,表现为下肢无力、肌酸激酶水平升高和难治性心肌萎缩。基因检测显示,她的PNPLA2基因存在c.32C>G(p.S11W)和c.516C>G(p.N172K)复合杂合变异,分别遗传自母亲和父亲。根据美国医学遗传学和基因组学学院(ACMG)的指南,这两个变异体被评为可能致病(PM1+PM2_支持+PP3+PP4):结论:PNPLA2 基因的 c.32C>G (p.S11W) 和 c.516C>G (p.N172K) 复合杂合变异可能是该患儿患重症肌无力和肌酸激酶升高的基础。
{"title":"[Clinical characteristics and genetic analysis of a child with Neutral lipid storage disease with myopathy].","authors":"Yu Zhang, Fenglei Guo, Nadan Lu, Miaomiao Tang, Dao Wang","doi":"10.3760/cma.j.cn511374-20220523-00312","DOIUrl":"10.3760/cma.j.cn511374-20220523-00312","url":null,"abstract":"<p><strong>Objective: </strong>To explore the clinical phenotype and genetic basis of a child with Neutral lipid storage disease with myopathy (NLSDM).</p><p><strong>Methods: </strong>A child who was admitted to the First Affiliated Hospital of Zhengzhou University in February 2021 for a history of elevated creatine kinase (CK) for over 2 months was selected as the study subject. Clinical and laboratory examinations were carried out, and the child was subjected to whole exome sequencing. Candidate variants were validated by Sanger sequencing of her family members.</p><p><strong>Results: </strong>The patient, a 9-year-old female, had exhibited weakness in the lower limbs, elevated CK level, and refractory cardiomyotrophy. Genetic testing revealed that she has harbored c.32C>G (p.S11W) and c.516C>G (p.N172K) compound heterozygous variants of the PNPLA2 gene, which were respectively inherited from her mother and father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as likely pathogenic (PM1+PM2_Supporting+PP3+PP4).</p><p><strong>Conclusion: </strong>The c.32C>G (p.S11W) and c.516C>G (p.N172K) compound heterozygous variants of the PNPLA2 gene probably underlay the myasthenia gravis and elevated creatine kinase in this child.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 7","pages":"840-843"},"PeriodicalIF":0.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471362","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 genetic variants and molecular pathogenesis in a Chinese pedigree affected with Multiple epiphyseal dysplasia]. [多发性骺发育不良中国血统的基因变异和分子发病机制分析]。
Q4 Medicine Pub Date : 2024-07-10 DOI: 10.3760/cma.j.cn511374-20230515-00286
Shan Li, Yueyang Sheng, Xinyu Wang, Ying Wang, Yanzhuo Zhang, Cheng'ai Wu, Xu Jiang

Objective: To analyze the genetic variant and molecular pathogenesis in a Chinese pedigree affected with Multiple epiphyseal dysplasia (MED).

Methods: A MED pedigree which had presented at the Beijing Jishuitan Hospital Affiliated to Capital Medical University on September 13, 2020 was selected as the study subject. Clinical data of the pedigree were collected. Peripheral blood samples were drawn from pedigree members for the extraction of genomic DNA. Whole exome sequencing (WES) was carried out for the pedigree. Candidate variant was verified by Sanger sequencing. Wild type and mutant SLC26A2 expression plasmids were constructed and transfected into human primary chondrocytes. The effect of the variants on the protein localization and cell proliferation was determined by immunofluorescence and CCK8 assays.

Results: WES and Sanger sequencing revealed that the proband has harbored compound heterozygous variants of the SLC26A2 gene, including a paternally derived c.484G>T (p.Val162Leu) missense variant and a maternally derived c.485_486delTG (p.Val162Glyfs*12) frameshifting variant. The SLC26A2WT and its mutant SLC26A2Val162Leu and SLC26A2Val162Glyfs*12 expression plasmids were distributed in the nuclei and cytoplasm of human primary chondrocytes. Compared with SLC26A2WT, the expressions of SLC26A2Val162Leu and SLC26A2Val162Glyfs*12 were decreased, along with reduced proliferation of human primary chondrocytes.

Conclusion: The c.484G>T and c.485_486delTG compound heterozygous variants of the SLC26A2 gene may affect the proliferation of human primary chondrocytes and underlay the pathogenesis of MED in this pedigree.

目的:分析多发性骺发育不良(MED)中国血统的遗传变异和分子发病机制:分析多发性骺发育不良(MED)中国血统的遗传变异和分子发病机制:方法:选取 2020 年 9 月 13 日在首都医科大学附属北京积水潭医院就诊的一个多发性骺发育不良(MED)家系作为研究对象。收集血统的临床数据。抽取血统成员的外周血样本以提取基因组 DNA。对该血统进行了全外显子组测序(WES)。通过桑格测序验证了候选变异。构建了野生型和突变型 SLC26A2 表达质粒,并将其转染到人类原代软骨细胞中。通过免疫荧光和 CCK8 检测确定了变体对蛋白定位和细胞增殖的影响:WES和Sanger测序结果显示,该患者的SLC26A2基因存在复合杂合变异,包括父源c.484G>T(p.Val162Leu)错义变异和母源c.485_486delTG(p.Val162Glyfs*12)移帧变异。SLC26A2WT 及其突变体 SLC26A2Val162Leu 和 SLC26A2Val162Glyfs*12 表达质粒分布在人原代软骨细胞的细胞核和细胞质中。与 SLC26A2WT 相比,SLC26A2Val162Leu 和 SLC26A2Val162Glyfs*12 的表达量减少,同时人原代软骨细胞的增殖也减少:结论:SLC26A2基因的c.484G>T和c.485_486delTG复合杂合变异可能影响人类原发性软骨细胞的增殖,是该血统中MED发病机制的基础。
{"title":"[Analysis of genetic variants and molecular pathogenesis in a Chinese pedigree affected with Multiple epiphyseal dysplasia].","authors":"Shan Li, Yueyang Sheng, Xinyu Wang, Ying Wang, Yanzhuo Zhang, Cheng'ai Wu, Xu Jiang","doi":"10.3760/cma.j.cn511374-20230515-00286","DOIUrl":"10.3760/cma.j.cn511374-20230515-00286","url":null,"abstract":"<p><strong>Objective: </strong>To analyze the genetic variant and molecular pathogenesis in a Chinese pedigree affected with Multiple epiphyseal dysplasia (MED).</p><p><strong>Methods: </strong>A MED pedigree which had presented at the Beijing Jishuitan Hospital Affiliated to Capital Medical University on September 13, 2020 was selected as the study subject. Clinical data of the pedigree were collected. Peripheral blood samples were drawn from pedigree members for the extraction of genomic DNA. Whole exome sequencing (WES) was carried out for the pedigree. Candidate variant was verified by Sanger sequencing. Wild type and mutant SLC26A2 expression plasmids were constructed and transfected into human primary chondrocytes. The effect of the variants on the protein localization and cell proliferation was determined by immunofluorescence and CCK8 assays.</p><p><strong>Results: </strong>WES and Sanger sequencing revealed that the proband has harbored compound heterozygous variants of the SLC26A2 gene, including a paternally derived c.484G>T (p.Val162Leu) missense variant and a maternally derived c.485_486delTG (p.Val162Glyfs*12) frameshifting variant. The SLC26A2WT and its mutant SLC26A2Val162Leu and SLC26A2Val162Glyfs*12 expression plasmids were distributed in the nuclei and cytoplasm of human primary chondrocytes. Compared with SLC26A2WT, the expressions of SLC26A2Val162Leu and SLC26A2Val162Glyfs*12 were decreased, along with reduced proliferation of human primary chondrocytes.</p><p><strong>Conclusion: </strong>The c.484G>T and c.485_486delTG compound heterozygous variants of the SLC26A2 gene may affect the proliferation of human primary chondrocytes and underlay the pathogenesis of MED in this pedigree.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 7","pages":"807-811"},"PeriodicalIF":0.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471358","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 of the -c.108C>T and c.192Q>R polymorphisms of the PON1 gene with preeclampsia among Chinese women]. [PON1基因的-c.108C>T和c.192Q>R多态性与中国妇女子痫前期的关系]。
Q4 Medicine Pub Date : 2024-07-10 DOI: 10.3760/cma.j.cn511374-20230515-00287
Xinyuan Zhang, Ping Fan, Qingqing Liu, Xinghui Liu, Huai Bai, Yujie Wu, Suiyan Li

Objective: To assess the association of -c.108C>T and c.192Q>R polymorphisms of paraoxonase 1 (PON1) gene with preeclampsia (PE) and the influence of genotypes on the metabolic and oxidative stress indexes among Chinese women.

Methods: This case-control study has included 334 patients with PE and 1337 healthy pregnant women. The -c.108C>T and c.192Q>R genotypes were determined by PCR and restriction fragment length polymorphism method. Metabolic and oxidative stress parameters were also analyzed.

Results: No statistical difference in the genotypic and allelic frequencies for the -c.108C>T and c.192Q>R polymorphisms of the PON1 gene was found between the PE patients and the healthy controls (P > 0.05). Nevertheless, the 192Q-108T haplotype of these polymorphisms was associated with an increased risk of PE (P = 0.007). Total antioxidant capacity (TAC) and atherosderosis index were higher in patients with the -108TT genotype compared with those with a CT genotype (P < 0.05); whilst total oxidant status was lower in patients with a CT genotype compared with those with a CC genotype (P = 0.036). Malondialdehyde level was higher in patients with a 192RR genotype compared with those with a QQ genotype (P = 0.019). TAC level was higher in patients with a RR genotype compared with those with a QR genotype (P = 0.015).

Conclusion: The 192Q-108T haplotype of the PON1 gene is associated with the risk for PE. These polymorphisms may be associated with abnormal lipid metabolism and oxidative stress among Chinese PE patients.

目的评估副氧合酶 1(PON1)基因-c.108C>T 和 c.192Q>R 多态性与子痫前期(PE)的相关性,以及基因型对中国女性代谢和氧化应激指标的影响:这项病例对照研究纳入了334名子痫前期患者和1337名健康孕妇。采用 PCR 和限制性片段长度多态性方法测定了-c.108C>T 和 c.192Q>R 基因型。同时还分析了代谢和氧化应激参数:结果:在 PE 患者和健康对照组之间,PON1 基因的 -c.108C>T 和 c.192Q>R 多态性的基因型和等位基因频率没有统计学差异(P > 0.05)。然而,这些多态性的 192Q-108T 单倍型与 PE 风险增加有关(P = 0.007)。与 CT 基因型患者相比,-108TT 基因型患者的总抗氧化能力(TAC)和动脉粥样硬化指数更高(P < 0.05);而与 CC 基因型患者相比,CT 基因型患者的总氧化状态更低(P = 0.036)。基因型为 192RR 的患者丙二醛水平高于基因型为 QQ 的患者(P = 0.019)。RR基因型患者的TAC水平高于QR基因型患者(P = 0.015):结论:PON1 基因的 192Q-108T 单倍型与 PE 风险有关。这些多态性可能与中国 PE 患者的脂质代谢异常和氧化应激有关。
{"title":"[Association of the -c.108C>T and c.192Q>R polymorphisms of the PON1 gene with preeclampsia among Chinese women].","authors":"Xinyuan Zhang, Ping Fan, Qingqing Liu, Xinghui Liu, Huai Bai, Yujie Wu, Suiyan Li","doi":"10.3760/cma.j.cn511374-20230515-00287","DOIUrl":"10.3760/cma.j.cn511374-20230515-00287","url":null,"abstract":"<p><strong>Objective: </strong>To assess the association of -c.108C>T and c.192Q>R polymorphisms of paraoxonase 1 (PON1) gene with preeclampsia (PE) and the influence of genotypes on the metabolic and oxidative stress indexes among Chinese women.</p><p><strong>Methods: </strong>This case-control study has included 334 patients with PE and 1337 healthy pregnant women. The -c.108C>T and c.192Q>R genotypes were determined by PCR and restriction fragment length polymorphism method. Metabolic and oxidative stress parameters were also analyzed.</p><p><strong>Results: </strong>No statistical difference in the genotypic and allelic frequencies for the -c.108C>T and c.192Q>R polymorphisms of the PON1 gene was found between the PE patients and the healthy controls (P > 0.05). Nevertheless, the 192Q-108T haplotype of these polymorphisms was associated with an increased risk of PE (P = 0.007). Total antioxidant capacity (TAC) and atherosderosis index were higher in patients with the -108TT genotype compared with those with a CT genotype (P < 0.05); whilst total oxidant status was lower in patients with a CT genotype compared with those with a CC genotype (P = 0.036). Malondialdehyde level was higher in patients with a 192RR genotype compared with those with a QQ genotype (P = 0.019). TAC level was higher in patients with a RR genotype compared with those with a QR genotype (P = 0.015).</p><p><strong>Conclusion: </strong>The 192Q-108T haplotype of the PON1 gene is associated with the risk for PE. These polymorphisms may be associated with abnormal lipid metabolism and oxidative stress among Chinese PE patients.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 7","pages":"866-871"},"PeriodicalIF":0.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471360","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
[Genetic analysis of a child with Dyschromatosis symmetrica hereditaria]. [对称性遗传色素沉着病患儿的基因分析]。
Q4 Medicine Pub Date : 2024-07-10 DOI: 10.3760/cma.j.cn511374-20230612-00352
Qian Ma, Lingyi Che, Xiangdong Kong

Objective: To investigate the clinical and genetic features of a child with Dyschromatosis symmetrica hereditaria (DSH) and variant of the ADAR1 gene.

Methods: A child who was admitted to the Department of Dermatology of the First Affiliated Hospital of Zhengzhou University in June 2020 due to irregular pigmented maculopapular rash on the dorsum of hands was selected as the study subject. Whole exome sequencing (WES) was carried out for the child and his similarly affected father, and Sanger sequencing was used to verify the candidate variant. SWISS-MODEL was used to predict the secondary and tertiary structures of the wild-type and mutant ADAR1 proteins.

Results: The child, a 13-year-old boy, had symmetrical hyperpigmented and depigmented spots on the back of his hands and was clinically diagnosed with DSH. WES and Sanger sequencing results showed that he and his father had both harbored a heterozygous c.2858dup (p.T954Dfs*20) truncating variant in exon 10 of the ADAR1 gene. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was predicted as pathogenic (PVS1+PM2_Supporting+PM1+PP3).

Conclusion: The c.2858dup (p.T954Dfs*20) variant of the ADAR1 gene probably underlay the DSH in this pedigree.

目的研究遗传性对称色素沉着病(Dyschromatosis symmetrica hereditaria,DSH)和ADAR1基因变异患儿的临床和遗传特征:方法:选取2020年6月因手背不规则色素斑丘疹入住郑州大学第一附属医院皮肤科的一名儿童作为研究对象。对该患儿及其类似患儿的父亲进行了全外显子组测序(WES),并使用 Sanger 测序来验证候选变异。研究人员利用 SWISS-MODEL 预测了野生型和突变型 ADAR1 蛋白的二级和三级结构:患儿是一名 13 岁男孩,手背上有对称性色素沉着斑和色素脱失斑,临床诊断为 DSH。WES和Sanger测序结果显示,他和他的父亲都在ADAR1基因第10外显子中携带杂合子c.2858dup (p.T954Dfs*20)截断变异。根据美国医学遗传学和基因组学学院的指南,该变异被预测为致病性(PVS1+PM2_Supporting+PM1+PP3):ADAR1基因的c.2858dup (p.T954Dfs*20)变异可能是该血统中DSH的基础。
{"title":"[Genetic analysis of a child with Dyschromatosis symmetrica hereditaria].","authors":"Qian Ma, Lingyi Che, Xiangdong Kong","doi":"10.3760/cma.j.cn511374-20230612-00352","DOIUrl":"10.3760/cma.j.cn511374-20230612-00352","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the clinical and genetic features of a child with Dyschromatosis symmetrica hereditaria (DSH) and variant of the ADAR1 gene.</p><p><strong>Methods: </strong>A child who was admitted to the Department of Dermatology of the First Affiliated Hospital of Zhengzhou University in June 2020 due to irregular pigmented maculopapular rash on the dorsum of hands was selected as the study subject. Whole exome sequencing (WES) was carried out for the child and his similarly affected father, and Sanger sequencing was used to verify the candidate variant. SWISS-MODEL was used to predict the secondary and tertiary structures of the wild-type and mutant ADAR1 proteins.</p><p><strong>Results: </strong>The child, a 13-year-old boy, had symmetrical hyperpigmented and depigmented spots on the back of his hands and was clinically diagnosed with DSH. WES and Sanger sequencing results showed that he and his father had both harbored a heterozygous c.2858dup (p.T954Dfs*20) truncating variant in exon 10 of the ADAR1 gene. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was predicted as pathogenic (PVS1+PM2_Supporting+PM1+PP3).</p><p><strong>Conclusion: </strong>The c.2858dup (p.T954Dfs*20) variant of the ADAR1 gene probably underlay the DSH in this pedigree.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 7","pages":"849-852"},"PeriodicalIF":0.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471367","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
期刊
中华医学遗传学杂志
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1