首页期刊导航|中华医学遗传学杂志
期刊信息/Journal information
中华医学遗传学杂志
四川大学
中华医学遗传学杂志

四川大学

张思仲

双月刊

1003-9406

cjmg@cma.org.cn

028-85501165

610041

四川省成都市人民南路三段17号(四川大学华西校区)

中华医学遗传学杂志/Journal Chinese Journal of Medical GeneticsCSCD北大核心CSTPCD
查看更多>>中华医学会主办，四川大学承办。本刊以报道我国医学遗传学、人类遗传学和相关领域的基础理论、技术方法等最新研究成果；以从事医学遗传学工作的各科临床医生、计划生育工作者、大专院校和科研单位有关人员为主要读者对象。设有述评、论著、技术与方法、综述、调查报告、遗传咨询、临床细胞遗传学、病例报告等栏目。 从1998年以来被美国《医学索引》（IM）、《化学文摘》（CA）、《工程索引》（EI）、ISI数据库的Biological Abstracts及BIOSIS Previews，波兰《哥白尼索引》（IC）,荷兰《医学文摘》（EM）和俄罗斯《文摘杂志》（AJ）等国际著名检索系统收录。
正式出版
收录年代

    容受前期与容受期子宫内膜基因表达及代谢物水平差异分析

    舒琴赵燕王岸聪李文...
    1496-1503页
    查看更多>>摘要：目的 分析容受前期和容受期子宫内膜基因表达及宫颈分泌物中氨基酸和肉碱水平差异，为探讨新的子宫内膜容受性分子标记物提供线索和依据。 方法 选取2020年1月6号至2022年1月31日就诊于临沂市人民医院生殖医学科的共59例不孕女性患者作为研究对象，收集临床资料。匹配年龄、体质量指数及不孕年限等因素选取准备胚胎移植的不孕女性3对(6名)，取内膜组织进行基因转录表达分析。另选经辅助生殖技术妊娠25例为对照组，门诊监测排卵未妊娠女性28例为病例组，采用超声判定内膜容受性状态。前者提取子宫内膜组织进行测序后，进行差异表达基因的GO数据库和KEGG数据库富集分析。后者取对照组和病例组宫颈分泌物，经质谱检测其中氨基酸和肉碱水平。采用秩和检验、t检验及χ2检验进行统计学分析。 结果 研究对象基本临床资料无明显差异(P>0.05)。基因测序提示上/下调最显著的基因分别是HLA-DRB5和MMP10。GO和KEGG富集差异表达基因较多的生物学过程、分子功能和通路主要有免疫调控、细胞粘附和色氨酸代谢等。分泌物代谢分析发现多种氨基酸和肉碱代谢物水平在二组间差异明显(P<0.05)，主要为氨基酸和肉碱水平如丙氨酸、缬氨酸、3-羟基丁酰肉碱(C4OH)+丙二酰肉碱(C3DC)/葵酰肉碱(C10)等。 结论 容受前期与容受期子宫内膜组织相比，基因转录表达差异显著，可能与子宫内膜容受性状态存在关联。氨基酸和肉碱水平提示差异变化较大指标可能作为标记物预测子宫内膜容受性状态。 Objective To analyze the difference in the gene expression, amino acid and carnitine levels in the cervical secretions between the endometria of pre-receptive and receptive stages, with an aim to provide clues for identifying new molecular markers for endometrial receptivity. Methods Fifty nine infertile women treated at the Department of Reproductive Medicine of Linyi People′s Hospital from January 6, 2020 to January 31, 2022 were selected as as the study subjects, which were matched with 3 pairs (6 cases) of infertile women preparing for embryo transfer based on factors such as age, body mass index, and length of infertility. Endometrial tissue samples were collected for gene transcription and expression analysis. Twenty five women who had become pregnant through assisted reproductive technology were selected as the control group, and 28 non-pregnant women receiving ovulation monitoring at the Outpatient Department were enrolled as the case group. Status of endometrial receptivity was determined by ultrasonography. In the former group, endometrial tissues were sampled for sequencing, and GO and KEGG database enrichment analysis of differentially expressed genes was carried out. In the latter group, cervical secretions were collected, and amino acid and carnitine levels were measured by mass spectrometry. Statistical analysis was carried out using rank sum test, t test and chi-square test with SPSS v25.0 software. Results No difference was found in the clinical data of the patients with regard to age, body mass index, infertility years, AMH, FSH, LH, E2, and type of infertility. Compared with the receptive endometrial tissues, there were 100 significantly up-regulated genes and 191 significantly down-regulated genes in the pre-receptive endometrial tissue, with the most significantly altered ones being HLA-DRB5 and MMP10. The biological processes, molecular functions and pathways enriched by more differentially expressed genes in GO and KEGG were mainly immune regulation, cell adhesion and tryptophan metabolism. Analysis of secretion metabolism also revealed a significant difference in the levels of amino acids and carnitine metabolites between the two groups (P < 0.05), in particular those of Alanine, Valine, 3-hydroxybutyrylcarnitine (C4OH) + malonylcarnitine (C3DC)/captoylcarnitine (C10). Conclusion A significant difference has been discovered in the levels of gene transcription and protein expression in the endometrial tissues from the pre-receptive and receptive stages. The levels of amino acids and carnitine, such as Alanine, Valine, 3-hydroxybutyryl carnitine (C4OH)+ malonyl carnitine (C3DC)/caproyl carnitine (C10), may be associated with the receptive status of the endometrium, though this need to be verified with larger samples.

    子宫内膜容受性转录组代谢组氨基酸肉碱

      原文链接:
    • 万方数据

    Menkes病一个家系的临床特征及 ATP7A基因变异分析

    张佳甘靖杨作臻王建军...
    1504-1507页
    查看更多>>摘要：目的 对1例Menkes患儿及其家系的临床特征及ATP7A基因变异进行分析，明确其致病原因，为临床诊断提供依据。 方法 选择2022年3月在四川大学华西第二医院确诊的1例Menkes患儿及其家系作为研究对象，分析其临床表现、实验室检查及ATP7A基因变异检测的结果。 结果 患儿主要表现为癫痫发作、全面发育落后，特殊面容、毛发稀疏、卷曲、乳酸、丙酮酸增高，铜兰蛋白明显降低；脑电图示多灶性尖、棘、多棘(慢)、多形性慢波频繁发放；头颅磁共振成像可见多发迂曲走行的血管影。全外显子组测序显示其ATP7A基因存在c.3076delA(p.Ile1026*)半合子变异，该变异遗传自母亲，可导致蛋白质翻译提前终止。根据美国医学遗传学与基因组学学会(ACMG)相关指南判定为致病变异(PVS1+PM2+PP4)。 结论 ATP7A基因c.3076del系新发变异，可能是本研究患儿的致病原因。基因检测为患儿的临床诊断提供了依据，并进一步丰富了ATP7A基因的变异谱。Menkes病患者的乳酸及丙酮酸水平显著升高，可用于指导诊断和管理。携带者的头发在显微镜下与患者相似，可能有助于诊断。 Objective To explore the clinical characteristics and variants of ATP7A gene in a child with Menkes disease. Methods A child with Menkes disease diagnosed at the West China Second Hospital of Sichuan University and its family members in March 2022 was selected as the study subjects. Clinical manifestations and results of laboratory tests and genetic testing were summarized. Results The main manifestations of the child included seizures, global development delay, facial dysmorphism, sparse and curly hair, increased lactate and pyruvate, and significantly decreased cuprin. EEG showed frequent issuance of multifocal spikes, spines, polyspines (slow) and polymorphic slow waves. Multiple tortuous vascular shadows were observed on cranial MRI. Whole exome sequencing revealed that the child has harbored a hemizygous c. 3076delA (p.ile1026*) variant of the ATP7A gene, which was inherited from his mother. The variant may lead to premature termination of protein translation. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted as pathogenic (PVS1+ PM2+ PP4). Conclusion The c. 3076delA (p.Ile1026*) variant of the ATP7A gene probably underlay the Menkes disease in this child. Above finding has provided evidence for clinical diagnosis. The significantly increased lactic acid and pyruvate can be used as a reference for the diagnosis and management of Menkes disease. Microscopic abnormalities in the hair of the carriers may also facilitate their diagnosis.

    癫痫全面性发育落后Menkes病ATP7A基因全外显子组测序

      原文链接:
    • 万方数据

    X连锁α-地中海贫血精神发育迟滞综合征一个家系的临床及 ATRX基因变异分析

    董睿杨亚丽郭辉高敏...
    1508-1511页
    查看更多>>摘要：目的 对1例表现为发育迟缓、特殊面容且具有阳性家族史的患儿进行临床和遗传学分析。 方法 以1例因"竖头不稳、不会翻身"于2020年就诊于山东大学附属儿童医院的患儿及其家庭作为研究对象。提取患儿及其父母及两个哥哥的基因组DNA，采用外显子区域捕获及高通量测序技术对其进行变异分析，对候选变异进行Sanger测序验证及家系分析。 结果 基因测序显示患儿及症状相似的哥哥均携带X染色体上的ATRX基因的c.5275C>A半合子变异，既往未见报道。经验证，其母亲为变异的杂合子携带者。患儿的父亲及未患病的哥哥均未携带上述变异。 结论 患儿及其患病的哥哥被确诊为罕见的X连锁α-地中海贫血精神发育迟滞综合征。c.5275C>A变异的发现丰富了ATRX基因的变异谱。 Objective To explore the clinical characteristics and genetic basis of two brothers featuring X-linked alpha thalassemia mental retardation (ATR-X) syndrome. Methods An infant who had presented at the Qilu Children′s Hospital in 2020 for unstable upright head and inability to roll over and his family were selected as the study subjects. The clinical features of the child and one of his brothers were summarized, and their genomic DNA was subjected to targeted capture and next generation sequencing (NGS). Results The brothers had presented with mental retardation and facial dysmorphisms. NGS revealed that they had both harbored a hemizygous c. 5275C>A variant of theATRX gene located on X chromosome, which was inherited from their mother. Conclusion The siblings were diagnosed with ATR-X syndrome. The discovery of the c. 5275C>A variant has enriched the mutational spectrum of theATRX gene.

    X连锁α-地中海贫血精神发育迟滞综合征发育迟缓ATRX基因

      原文链接:
    • 万方数据

    F12基因复合变异导致的遗传性凝血因子Ⅻ缺陷症一个家系的分析

    程晓丽杨婷杨柳辛毅娟...
    1512-1516页
    查看更多>>摘要：目的 对1个遗传性凝血因子Ⅻ(FⅫ)缺陷症家系进行临床表型及基因变异分析。 方法 以2021年12月24日空军军医大学第一附属医院检验科发现的1个FⅫ缺陷症家系作为研究对象。用凝固法检测活化部分凝血活酶时间(APTT)与凝血因子Ⅻ的活性(FⅫ：C)，用ELISA法检测FⅫ抗原(FⅫ：Ag)。提取基因组DNA，用Sanger法测定F12基因的所有外显子及其侧翼序列。用ClustalX-2.1-win、PROVEAN及Swiss-Pdb Viewer软件分析变异位点氨基酸的保守性、变异的有害性以及对蛋白质结构的影响。 结果 先证者APTT延长至70.2 s，FⅫ：C和FⅫ：Ag分别降低至12%和13%。基因测序发现先证者F12基因第5和13外显子分别存在c.346G>A(p.Gly97Ser)和c.1583C>A(p.Ser509Tyr)杂合错义变异；其父亲和姐姐均携带c.346G>A(p.Gly97Ser)杂合变异，母亲和哥哥均携带c.1583C>A(p.Ser509Tyr)杂合变异。 结论 c.346G>A(p.Gly97Ser)和c.1583C>A(p.Ser509Tyr)复合杂合变异很可能是该家系遗传性FⅫ缺陷症的遗传学病因。 Objective To analyze the clinical phenotypes and genetic variants of a Chinese pedigree affected with Hereditary coagulation factor Ⅻ (FⅫ) deficiency. Methods A pedigree presented at the First Affiliated Hospital of Air Force Medical University on December 24, 2021 was selected as the study subject. Activated partial thromboplastin time (APTT) and coagulation factor Ⅻ activity (FⅫ: C) were determine by a clotting method, and FⅫ antigen was detected with an ELISA assay. Following the extraction of genomic DNA, all exons and flanking regions of the F12 gene were subjected to Sanger sequencing. Clustalx-2.1-win, PROVEAN and Swiss-PDB Viewer software was used to analyze the conservation of amino acids at the variant sites, impact of of the variants on the amino acid substitutions and the protein structure. Results The APTT of the proband has prolonged to 70.2 s. Her FⅫ: C and FⅫ: Ag have decreased to 12% and 13%, respectively. DNA sequencing revealed that the proband has harbored c. 346G>A (p.Gly97Ser) and c. 1583C>A (p.Ser509Tyr) heterozygous compound missense variants in exons 5 and 13 of theF12 gene, respectively. Her father and sister were heterozygous carriers for the c. 346G>A (p.Gly97Ser) variant, whilst her mother and brother were heterozygous for the c. 1583C>A (p.Ser509Tyr) variant. Conclusion The c. 346G>A (p.Gly97Ser) and c. 1583C>A (p.Ser509Tyr) compound heterozygous variants of theF12 gene probably underlay the pathogenesis of hereditary coagulation FⅫ deficiency in this pedigree.

    凝血因子Ⅻ错义变异家系遗传性FⅫ缺陷症

      原文链接:
    • 万方数据

    IRF6基因变异所致van der Woude综合征一个家系的遗传学分析

    朱湘玉曹培暄朱雨捷李洁...
    1517-1520页
    查看更多>>摘要：目的 探讨1个van der Woude综合征(VWS)家系的遗传学特征，并为其提供生育指导。 方法 选取2020年5月因"2次唇腭裂儿妊娠史"在南京鼓楼医院就诊的1例先证者及其家系成员为研究对象。应用家系全外显子组测序(trio-WES)对先证者及其父母进行致病变异筛选，针对候选致病变异进行Sanger测序家系验证(4代共8人)和生物信息学分析。对该家系中的胎儿进行染色体微阵列分析(CMA)以排除拷贝数变异。 结果 Trio-WES发现先证者及其父亲携带IRF6: c.742G>T(p.G248C)杂合变异，其母亲该位点为野生型。该变异为错义变异，位于重要的蛋白质功能结构区，在正常参考人群基因数据库中未见报道，多种软件预测该变异影响蛋白质结构/功能的可能性较大，与该家系中患者特异性表型高度相关，且Sanger测序结果显示家系中8名成员(包括3名患者)的基因型与表型共分离。依据美国医学遗传学与基因组学学会(ACMG)相关指南，评估为可能致病性变异(PM1+PM2_Supporting+PP1+PP3+PP4)。据此结果对先证者进行植入前遗传学诊断，生育表型正常后代，位点检测及CMA均未见异常。 结论 本研究明确了IRF6 c.742G>T(p.G248C)杂合变异为该家系的遗传学病因，并为先证者提供了生育指导。 Objective To explore the genetic characteristics of a Chinese pedigree affected with van der Woude syndrome (VWS). Methods A proband who had visited the Drum Tower Hospital Affiliated to Nanjing University Medical School in May 2020 for "two previous pregnancies with cleft lip and palate" was selected as the study subject. Trio-whole exome sequencing (trio-WES) was carried out for the patient. Candidate variants were verified by Sanger sequencing of her pedigree members (8 individuals from four generations) and bioinformatic analysis. Chromosomal microarray analysis (CMA) was used to rule out copy number variations in the fetuses. Results Trio-WES revealed that the proband and her father had both harbored a heterozygous c. 742G>T (p.G248C) missense variant of theIRF6 gene, for which her mother was of the wild type. The variant was located in a region with important functions and has not been reported previously. Prediction with several software suggested that it is likely to have a significant impact on the protein structure/function and is highly correlated with the specific phenotypes in this pedigree. Sanger sequencing confirmed co-segregation of the genotypes and phenotypes in the pedigree. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), this variant was rated as likely pathogenic (PM1+ PM2_Supporting+ PP1+ PP3+ PP4). Based on the above results, pre-implantation genetic diagnosis was carried out for the proband, which has led to birth of a healthy offspring with normal results for both site testing and CMA. Conclusion The IRF6: c. 742G>T (p.G248C) heterozygous variant probably underlay the VWS in this pedigree. Above finding has also enabled reproductive guidance for the proband.

    唇腭裂VanderWoude综合征IRF6基因全外显子组测序基因测序

      原文链接:
    • 万方数据

    结节性硬化症患儿2例的临床特征及遗传学分析

    李林飞罗淑颖张耀东尚清...
    1521-1525页
    查看更多>>摘要：目的 探讨2例结节性硬化症(TSC)患儿的临床表现及基因变异特点。 方法 选取2020年6月至2021年7月于郑州大学附属儿童医院就诊的2例TSC患儿为研究对象。收集2例患儿的临床资料，采用全外显子组测序(WES)筛选患儿的致病基因，针对可疑变异位点，进行Sanger测序家系验证。 结果 患儿1为7月29日龄男性，患儿2为2岁6月龄男性。2例患儿均表现为癫痫发作和多发性色素脱失斑。基因检测结果显示2例患儿分别携带TSC2基因c.3239_3240insA和c.3330delC新发变异，既往均未见报道，根据美国医学遗传学和基因组学学会相关指南，均评级为致病性变异(PVS1+PS2+PM2_Supporting)。 结论 本研究明确2例TSC患儿的遗传学病因，丰富了中国人群TSC的表型和基因变异谱。 Objective To explore the clinical characteristics and genetic variants in two children with Tuberous sclerosis complex (TSC). Methods Two children who had presented at the Children′s Hospital Affiliated to Zhengzhou University respectively in June 2020 and July 2021 were selected as the study subjects. Clinical data of the children were collected, and potential pathogenic variants were screened by whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing of their family members. Results Child 1 was a 7-month-and-29-day-old male, and child 2 was a 2-year-and-6-month-old male. Both children had shown symptoms of epileptic seizures and multiple hypomelanotic macules. Genetic testing revealed that both children had harbored de novo variants of the TSC2 gene, namely c. 3239_3240insA and c. 3330delC, which were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as pathogenic (PVS1+ PS2+ PM2_Supporting). Conclusion This study has uncovered the genetic etiology for two children with TSC. Above findings have also enriched the phenotypic and mutational spectrum of TSC in the Chinese population.

    结节性硬化症TSC2基因新发变异

      原文链接:
    • 万方数据

    MC2R基因变异致家族性糖皮质激素缺乏症1型患儿2例的临床特征与遗传学病因分析

    高静刘晓景崔岩曹冰燕...
    1526-1530页
    查看更多>>摘要：目的 提高临床医师对黑皮质素2受体(MC2R)基因变异导致的家族性糖皮质激素缺乏症1型(FGD1)的认识，减少漏诊与误诊。 方法 回顾性分析2019年至2021年于河南省儿童医院收治的2例FGD1患儿的临床资料、基因检测结果、治疗和随访结果。 结果 全外显子组测序结果提示患儿1携带MC2R基因c.433C>T(p.R145C)与c.710T>C(p.L237P)复合杂合变异，患儿2携带MC2R基因c.145delG(p.V49Cfs*35)和c.307G>A(p.D103N)复合杂合变异，其中c.710T>C(p.L237P)与c.145delG(p.V49Cfs*35)变异为新发现的变异位点。 结论 FGD1临床罕见，基因检测是确诊的关键。新变异位点的检出丰富了MC2R基因的变异谱。 Objective To improve the recognition of Familial glucocorticoid deficiency type 1 (FGD1) due to variants of melanocortin 2 receptor (MC2R) gene. Methods Two children with FGD1 diagnosed at the Henan Children′s Hospital respectively in 2019 and 2021 were selected as the study subjects. Clinical data, treatment, follow-up and results of genetic testing were collected and retrospectively analyzed. Results Whole exome sequencing revealed that both children had harbored compound heterozygous variants of the MC2R gene, including c. 433C>T (p.R145C) and c. 710T>C (p.L237P) in child 1, and c. 145delG (p.V49Cfs*35) and c. 307G>A (p.D103N) in child 2, among which c. 710T>C (p.L237P) and c. 145delG (p.V49Cfs*35) were unreported previously. Conclusion FGD1 is clinically rare, and genetic sequencing is crucial for the definite diagnosis. Discovery of the and novel variants has enriched the mutational spectrum of the FGD1 gene.

    家族性糖皮质激素缺乏症黑皮质素2受体促肾上腺皮质激素氢化可的松

      原文链接:
    • 万方数据

    TGFBR2基因变异所致Loeys-Dietz综合征患者1例的临床表现及遗传学分析

    王月丽孔志华万珑王傲雪...
    1531-1535页
    查看更多>>摘要：目的 对1例临床疑似为Loeys-Dietz综合征(LDS)的患者行全外显子组测序，明确其遗传学病因。 方法 将1例2018年9月就诊于首都医科大学附属北京安贞医院的患者作为研究对象，完善其临床资料及既往病史。采集患者及父母的外周血样，对其进行全外显子组测序，重点分析与遗传性主动脉瘤疾病相关的基因。并通过Sanger测序对候选变异进行家系验证。 结果 患者临床检查及既往病史均提示存在早发性主动脉扩张及夹层等心血管异常，临床疑似为LDS。二代测序发现其TGFBR2基因存在c.1526G>T(p.Gly509Val)杂合错义变异，其父母未携带相同变异。根据美国医学遗传学与基因组学学会(ACMG)相关指南判定为疑似致病变异(PM1+PM2_Supporting+PM6+PP3+PP4)。 结论 TGFBR2基因c.1526G>T变异可能是该患者的遗传学病因，国内既往未见报道。上述结果丰富了LDS患者TGFBR2基因的变异谱，为患者的临床诊断和遗传咨询提供了依据。 Objective To explore the genetic basis of a patient with clinically suspected Loeys-Dietz syndrome (LDS). Methods A child who was presented at Beijing Anzhen Hospital in September 2018 was selected as the study subject. Clinical data and family history of the patient were collected, along with peripheral blood samples of the proband and his parents. Whole exome sequencing (WES) was carried out through next-generation sequencing. Candidate variants were searched through bioinformatic analysis focusing on genes associated with hereditary aortic aneurysms. Candidate variant was verified by Sanger sequencing. Results The patient was found to have cardiovascular abnormalities including early-onset aortic dilatation and coarctation, and LDS syndrome was suspected. WES revealed that he has harbored a heterozygous c. 1526G>T missense variant of theTGFBR2 gene. The same variant was not found in either parent and was predicted as likely pathogenic (PM1+ PM2_Supporting+ PM6+ PP3+ PP4) based on the guidelines from the American College for Medical Genetics and Genomics (ACMG). Conclusion The TGFBR2 c. 1526G>T variant probably underlay the LDS in this patient and was unreported previously in China. Above finding has enriched the mutational spectrum of theTGFBR2 gene associated with the LDS and provided a basis for the genetic counseling for the patient.

    Loeys-Dietz综合征TGFBR2基因基因检测

      原文链接:
    • 万方数据

    PUF60基因变异所致Verheij综合征患儿1例的分析

    王红英盛茂邱文娜周丽君...
    1536-1540页
    查看更多>>摘要：目的 分析1例Verheij综合征(VRJS)患儿的临床表型与基因变异，并探讨二者的相关性。 方法 选取2022年7月因"自幼高肩胛骨"就诊于苏州大学附属儿童医院骨科门诊和苏州市吴江区儿童医院多学科门诊的1例患儿作为研究对象。采集患儿及其父母的外周血样，对其进行全外显子组测序分析，并对候选变异进行Sanger测序验证。 结果 患儿表现为高肩胛骨、斜颈、上肢及肩关节活动受限、面容异常、皮肤散在咖啡斑，智力发育障碍等。测序结果显示其携带PUF60基因c.405dupT(p.Ile136Tyrfs*4)新发杂合变异。根据美国医学遗传学与基因组学学会(ACMG)相关指南判定为致病性(PVS1+PS2_moderate+PM2_supporting)。结合患儿的临床表型及基因检测结果，确诊其为PUF60基因c.405dupT变异所致的VRJS。 结论 VRJS临床表现为特殊面容、智力障碍及高肩胛骨、椎体横突融合畸形、肩椎骨形成等骨骼发育异常，心脏、肾脏、眼等部位无明显异常，不易与Klippel-Feil综合征相区别。本研究丰富了PUF60基因的变异谱，为明确VRJS基因型与表型的相关性提供了数据。 Objective To explore the clinical phenotype and genetic variant in a child with Verheij syndrome (VRJS). Methods A child who had presented at the Soochow University Affiliated Children′s Hospital and Wujiang District Children′s Hospital in July 2022 for "elevated scapula since early childhood" was selected as the study subject. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. Results The child had manifested elevated scapulae, torticollis, neck asymmetry, facial dysmorphism, dispersed café-au-lait spots, limited mobility of upper limbs and shoulder joints, and intellectual disability. Sequencing revealed that he has harbored a de novo heterozygous c. 405dupT (p.Ile136Tyrfs*4) variant of the PUF60 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), this variant was classified as pathogenic (PVS1+ PS2_moderate+ PM2_supporting). Combined his clinical features and result of genetic testing, the child was diagnosed with VRJS due to variant of the PUF60 gene. Conclusion The clinical manifestations of VRJS include facial dysmorphism, intellectual disability, elevated scapulae, vertebral fusion, other skeletal malformations, without significant abnormalities of the heart, kidney, and eyes, which need to be distinguished from Klippel-Feil syndrome. Above finding has expended the mutation spectrum of the PUF60 gene and provided a reference for delineation of the genotype-phenotype correlation of the VRJS.

    Verheij综合征PUF60基因骨骼发育畸形椎体融合

      原文链接:
    • 万方数据

    TUBB基因p.M73V变异所致复合型脑皮质发育不良伴其他脑发育畸形6型患儿1例的遗传学分析

    薛慧琴唐巧茵郭荣曹桂芝...
    1541-1545页
    查看更多>>摘要：目的 探讨1例多发畸形患儿的遗传学病因。 方法 以2021年2月就诊于山西省儿童医院的1例患儿作为研究对象。收集患儿的临床信息，并对其进行全外显子组测序(WES)，对候选变异进行Sanger测序家系验证以及致病性分析。 结果 患儿全身皮肤无异常，但存在右耳缺如、半椎体畸形，心室间隔缺损、动脉导管与卵圆孔未闭、左肾集合系统分离等。磁共振成像显示双侧侧脑室不规则增大、大脑皮层与颞侧脑膜间距增加。测序发现其携带TUBB基因NM_178014.4: c.217A>G(p.Met73Val)新发杂合变异，根据美国医学遗传学与基因组学学会(ACMG)相关指南判定为可能致病。结合其临床表型以及基因检测结果，患儿被确诊为复合型脑皮质发育不良伴其他脑发育畸形6型(CDCBM6)。 结论 CDCBM是一类罕见的具有遗传异质性的严重疾病，其中TUBB基因缺陷所致的CDCBM6更为罕见。本研究的结果扩展了TUBB基因的变异谱和表型谱，为总结CDCBM6的基因型-表型对应关系提供了重要的参考。 Objective To explore the genetic basis for a child with multiple malformations. Methods A child who had presented at Shanxi Provincial Children′s Hospital in February 2021 was selected as the study subject. Clinical data of the patient was collected, and whole exome sequencing (WES) was carried out to screen pathogenic variants associated with the phenotype. Candidate variant was validated by Sanger sequencing of her family members. Results The child had normal skin, but right ear defect, hemivertebral deformity, ventricular septal defect, arterial duct and patent foramen ovale, and separation of collecting system of the left kidney. Cranial MRI showed irregular enlargement of bilateral ventricles and widening of the distance between the cerebral cortex and temporal meninges. Genetic testing revealed that she has harbored a heterozygous variant of NM_178014.4: c. 217A>G (p.Met73Val) in theTUBB gene, which was unreported previously and predicted to be likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). The child was diagnosed with Complex cortical dysplasia with other brain malformations 6 (CDCBM6). Conclusion CDCBM is a rare and serious disease with great genetic heterogeneity, and CDCBM6 caused by mutations of the TUBB gene is even rarer. Above finding has enriched the variant and phenotypic spectrum of the TUBB gene, and provided important reference for summarizing the genotype-phenotype correlation of the CDCBM6.

    TUBB基因复合型脑皮质发育不良伴其他脑发育畸形先天性对称皮肤褶皱综合征

      原文链接:
    • 万方数据