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国际遗传学杂志
哈尔滨医科大学
国际遗传学杂志

哈尔滨医科大学

傅松滨

双月刊

1673-4386

genetics2006@163.com

0451-86662947

150081

黑龙江省哈尔滨市南岗区保健路157号

国际遗传学杂志/Journal International Journal of Genetics北大核心CSTPCD
查看更多>>1978年创刊，中华人民共和国卫生部主管，中华医学会、哈尔滨医科大学主办。本刊前身是《国外医学，遗传学分册》，是公开发行的国家级学术期刊。为从事遗传学以及相关学科、交叉学科的科研、教学和广大的临床医务工作者提供参考。
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    综合性携带者筛查关键问题专家共识(2024版)

    卢大儒安宇沈亦平
    1-11页
    查看更多>>摘要：综合性携带者筛查是一项针对没有明显遗传病表型，但可能携带遗传病基因致病变异的个体进行的筛查性检测。与常规携带者筛查的区别是，综合性携带者筛查的疾病不仅包括隐性遗传病，也包括具有临床干预意义的成年显性遗传病。综合性携带者筛查旨在提前发现中度及以上严重程度遗传病的生育高风险夫妻和患病高风险个体，为遗传咨询、生殖决策、疾病预防和管理提供依据，减少由遗传病带来的家庭和社会经济负担，提高人群健康水平。目前，携带者筛查相关指南和共识主要涉及常染色体隐性和X连锁遗传病。为介绍和规范综合性携带者筛查的应用，中国遗传学会遗传诊断分会和上海市遗传学会临床遗传与遗传咨询专委会组织部分专家，结合国内外最新进展，制定本共识。共识讨论了综合性携带者筛查的定义和目的、适用人群、筛查基因和疾病的选择原则、筛查策略、报告原则和遗传咨询等关键问题，供政策制定者、临床工作者、检测机构和民众参考。 Comprehensive carrier screening (CCS) is a screening test performed on individuals without overt phenotype for genetic disorders but who might have pathogenic variants in disease genes. Currently existing guidelines and consensus for carrier screening mainly focus on autosomal recessive and X-linked genetic disorders, CCS expands its scope beyond these conditions to include dominant conditions with clinical actionability in adulthood. Thus, the goal of CCS is to proactively identify not only at-risk couples of having offspring with moderate to profound genetic disorders, but also at-risk individuals being affected by these disorders. Therefore, CCS serves as a more comprehensive basis for genetic counseling, reproductive decision-making, disease prevention and management, which in turn can better serve the purpose of reducing the familial and socio-economic burdens associated with genetic disorders and improving the overall health of general population. To introduce and standardize the implementation of CCS, the Genetics Diagnosis Branch of Chinese Genetic Society and the Clinical Genetics and Genetic Counseling Committee of Shanghai Society of Genetics organized an expert panel to develop this consensus. The consensus covers key issues related to CCS, including its definition and purpose, the target population, criteria for designing screening panel, screening strategies, reporting guidelines, and genetic counseling. This consensus serves as a reference for policymakers, healthcare professionals, laboratory geneticists, and the general public.

    综合性携带者筛查显性遗传病隐性遗传病专家共识

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    孕妇外周血胎儿游离DNA检测失败的因素与重复检测结果分析

    王瑞吴秋华王晓斌刘瑗...
    12-17页
    查看更多>>摘要：目的 探讨孕妇外周血胎儿游离DNA(cell-free fetal DNA，cffDNA)检测全流程中导致检测失败的因素以及实验室内重复检测的策略及结果。 方法 收集2021年2月至2022年12月在西北妇女儿童医院医学遗传中心就诊并接受外周血cffDNA检测的孕妇36 301例，根据实验室内质控要求和流程进行重复检测。对孕妇外周血cffDNA检测失败的因素和重复检测的结果进行分析。 结果 36 301例接受外周血cffDNA检测孕妇中，首次检测未取得有效结果需要重复检测孕妇999例，重复检测率为2.75%(999/36 301)。孕妇外周血cffDNA检测整个流程中，样本需要重复检测的主要原因是测序后存在单条染色体数据波动，重复检测后有92.99%(929/999)的样本得到有效结果，其中85.69%(856/999)为低风险，7.31%(73/999)为高风险，7.01%(70/999)再次检测失败，孕妇外周血cffDNA检测失败率为0.19%(70/36 301)。最终检测失败的主要原因也是单条染色体数据波动。 结论 在严格的实验质量管理与控制下，孕妇外周血cffDNA检测失败是客观存在且不可避免的，检测前要做好遗传咨询告知。测序后存在单条染色体数据波动是检测失败的主要原因，重复检测成功率较高，可有效提高最终检测成功率。 Objective To explore the factors leading to test failure in the whole process of cell-free fetal DNA (cffDNA) in pregnant women and the strategy and result of repeated testing in the laboratory. Methods CffDNA testing was performed on 36 301 pregnant women who came to Center of Medical Genetics of Northwest Women’s and Children’s Hospital from February 2021 to December 2022. Repeat testing was performed according to the laboratory quality control requirements and procedures. Factors contributing to failure to perform maternal peripheral blood cffDNA testing and results of repeat testing were analyzed. Results Among the 36 301 samples who received maternal peripheral blood cffDNA test, 999 samples required repeat test without the first effective results, and the repeat test rate was 2.75% (999/36 301). In the whole process of maternal peripheral blood cffDNA testing, the main reason is that samples had single chromosome data fluctuations after sequencing, 92.99% (929/999) of samples obtained effective results after repeated testing, of which 85.69% (856/999) were low risk, 7.31% (73/999) were high risk, 7.01% (70/999) failed again. Pregnant peripheral blood cffDNA failure rate was 0.19% (70/36 301). The main reason for the failure of the final detection is also the fluctuation of the single chromosome data. Conclusion Under the strict experimental quality management and control, the failure of peripheral blood cffDNA test of pregnant women is objective and inevitable, and genetic counseling should be done before testing. The fluctuation of single chromosome data after sequencing is the main reason for detection failure. The high success rate of repeated detection can effectively increase the final success rate of repeated detection.

    产前筛查无创产前检测(NIPT)胎儿游离DNA检测失败

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    DNMT3A基因胚系变异相关遗传性疾病及分子机制研究进展

    赵桂玉刘月芳
    18-23页
    查看更多>>摘要：DNMT3A胚系突变可引起两种遗传性疾病即Tatton-Brown-Rahman综合征(Tatton-Brown-Rahman syndrome，TBRS)和Heyn-Sproul-Jackson综合征，这两种疾病表型部分相反但是其潜在分子机制尚未完全阐明。本综述主要对DNMT3A基因胚系变异导致这两组疾病的分子机制研究进展进行综述。在TBRS中，DNMT3A基因PWWP功能域变异主要通过抑制其在H3K36me2富集区域定位降低mCpG水平，在神经系统，DNMT3A基因变异还可降低mCpA水平从而抑制MeCP2的结合。在Heyn-Sproul-Jackson综合征中，DNMT3A基因PWWP功能域的另外一些位点变异不仅抑制其在H3K36me2富集区域定位，同时还增强其在H2AK119ub区域富集。对DNMT3A基因变异导致出生缺陷的分子机制充分研究对该类疾病的靶向治疗具有重要意义。 Germline variants of DNMT3A define Tatton-Brown-Rahman syndrome (TBRS) and Heyn-Sproul-Jackson syndrome, which have opposite clinical features but the underlying molecular mechanisms have not been fully elucidated.This review mainly reviews the progress of research on the molecular mechanisms of TBRS and Heyn-Sproul-Jackson syndrome. In TBRS, the variants in DNMT3A PWWP domain mainly reduces mCpG levels by inhibiting its localization in H3K36me2-enriched regions.In the nervous system, DNMT3A gene variants can also reduce mCpA levels and inhibit MeCP2 binding. In Heyn-Sproul-Jackson syndrome, some variants in DNMT3A PWWP domain not only inhibited its localization in the H3K36me2-enriched region, but also enhanced its enrichment in the H2AK119ub region. Understanding the mechanisms of birth defects caused by DNMT3A germline variants may guide the design of targeted therapy.

    DNMT3A基因出生缺陷Tatton-Brown-Rahman综合征Heyn-Sproul-Jackson综合征NSD1基因MeCP2基因

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    骨性关节炎的遗传学研究进展

    杨芳军王富洋谢银银张倩...
    24-31页
    查看更多>>摘要：骨性关节炎(osteoarthritis，OA)的发病率日益增长，已成为最常见的退行性关节疾病。由于OA的生物学复杂性，对于病因及发病机制还没有完全理解。这篇叙述性综述的目的是重点介绍最近5年发表的OA遗传学的关键研究文章，通过介绍出现的新技术、新方法揭示这些变异基因在OA病因及发病机制中的作用。通过全基因组关联研究(genome wide association study，GWAS)和孟德尔随机化研究(Mendelian randomization, MR)总结OA与其他疾病、常见风险因素的遗传相关性，为OA的诊断、治疗及预防提供新方法。 The incidence of osteoarthritis (OA) is increasing and it has become the most common degenerative joint disease. Due to the biological complexity of OA, the etiology and pathogenesis of OA are not fully understood. The purpose of this narrative review is to highlight the key research articles on OA genetics published in the last 5 years, and to reveal the role of these variants in the etiology and pathogenesis of OA by introducing new technologies and methods. To explore the genetic correlation between OA and other diseases and common risk factors through genome wide association study (GWAS) and Mendelian randomization study (MR), and to provide new methods for the diagnosis, treatment and prevention of OA.

    骨性关节炎遗传学流行病学

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    RRM2B基因复合杂合突变致线粒体DNA耗竭综合征2例家系临床特征及遗传学分析

    莫李媚羊芳菲赵丽姚如恩...
    32-39页
    查看更多>>摘要：目的 探讨RRM2B基因突变致线粒体DNA耗竭综合征(mitochondrial DNA depletion syndrome，MDDS)的临床特征及遗传信息。 方法 对可疑患儿进行全外显子测序筛查潜在的基因变异，Sanger测序进行家系验证，同时采用ClinVar数据库和REVEL等软件预测核苷酸、氨基酸变异对蛋白功能的影响。通过文献检索，对已报道的RRM2B基因突变患者的遗传资料进行分析，并对RRM2B基因突变的类型和频率进行评估。 结果 患儿，女，6个月24天，临床上表现为发育倒退、肌张力低下、呼吸衰竭、腹泻等症状，实验室检查提示乳酸酸中毒、肌酶增高，测序结果显示患儿RRM2B基因存在c.125T>G(p.Phe42Cys)和c.175G>C (p.Ala59Pro)复合杂合突变，分别遗传自其母亲和父亲，患儿哥哥临床症状相同，也同样携带该基因复合杂合突变。文献数据库未见c.125T>G(p.Phe42Cys)位点变异的相关文献报道，2022年有1例报道c.175G>C (p.Ala59Pro)位点突变，根据美国医学遗传学与基因组学学会指南，判定为可能致病性变异。RRM2B基因突变目前报道共105例患者62种变异(包含本研究纳入的2例患者)，外显子E6和E9是突变热点，突变类型以错义突变多见。 结论 RRM2B基因c.125T>G(p.Phe42Cys)和c.175G>C (p.Ala59Pro)杂合突变是导致MDDS的突变位点，本研究结果加强了对该类疾病的临床特征和遗传性病因认识，同时扩展了RRM2B基因变异谱。 Objective The purpose of this research is to investigate the clinical features and genetic information associated with mitochondrial DNA depletion syndrome (MDDS) caused by RRM2B gene mutation. Methods Whole-exome sequencing was performed to screen for potential genetic variation in suspicious children and Sanger sequencing was performed for family verification. Meanwhile, ClinVar database and REVEL software were used to predict the effect of nucleotide and amino acid variation on protein function. The genetic data of patients with RRM2B gene mutations were analyzed by literature search and the types and frequencies of RRM2B gene mutations were evaluated. Results The baby girl was six months and twenty-four days old. The clinical symptoms were regressive growth, hypotonia, respiratory failure, diarrhea and so on. Laboratory examination suggested lactic acidosis and increased muscle enzymes. Sequencing revealed that the child has carried compound heterozygous missense variants of the RRM2B gene, namely c. 125T>G (p. Phe42Cys) and c. 175G>C (p.Ala59Pro), which were respectively inherited from her mother and father, and both were likely pathogenic variants. The mutations of c. 125T>G (p.Phe42Cys) was newly discovered mutation. Her older brother had the same clinical features and mutation. Sixty-two mutations inRRM2B gene were reported in 105 patients (including two patients included in this study). Exon 6 and Exon 9 were hot spots mutation and missense mutations were common. Conclusion The c. 125T>G(p.Phe42Cys) and c. 175G>C(p.Ala59Pro) compound heterozygous mutations ofRRM2B gene may be the pathogenic genes of MDDS. The results of this study has strengthened the understanding of the clinical features and genetic etiology of this disease and expanded the mutation spectrum of the RRM2B gene.

    线粒体DNA耗竭综合征RRM2B基因乳酸酸中毒核糖核苷酸还原酶

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    常染色体隐性遗传表皮松弛症患者的 PYCR1基因纯合变异分析与生育咨询

    张艳林堃曾丽娜林荔...
    40-45页
    查看更多>>摘要：目的 对1例常染色体隐性遗传表皮松弛症患者的PYCR1基因进行变异分析，明确其遗传学病因。 方法 收集患者的外周静脉血进行染色体核型分析、单核苷酸多态性微阵列芯片(single nucleotide polymorphism array，SNP-array)分析及全外显子测序(whole exome sequencing，WES)，并通过Sanger测序进行位点验证。 结果 患者的外周静脉血中检测到PYCR1基因的4号外显子存在1个来源未知的纯合变异c．345delC(p.R116Gfs*6)，为移码突变，目前，国内尚未见报道。 结论 PYCR1基因的4号外显子c.345delC(p.R116Gfs*6)纯合变异为患者表皮松弛的病因，为其后续生育提供了遗传学依据。 Objective To analyze the variations in the PYCR1 gene of a patient with autosomal recessive inherited cutis laxa. Methods Chromosome karyotyping analysis, SNP-array and WES were performed on blood samples. Candidate variants were verified by Sanger sequencing. Results A homozygous mutation c. 345delC(p.R116Gfs*6) was identified in exon 4 of the PYCR1 gene through WES, which is a frame shift mutation. At present, no studies have reported it in China. Conclusion The homozygous mutation c. 345delC(p.R116Gfs*6) variant in exon4 of the PYCR1 is pathogenic cause of cutis laxa. It provide genetic basis for future reproduction.

    表皮松弛症PYCR1基因全外显子检测Sanger测序

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    15q11.2-q14新发额外标记染色体嵌合重复患儿临床表型及遗传学分析

    张新艳陈玉清张爽张健...
    46-54页
    查看更多>>摘要：目的 明确1例智力低下、发育异常、语言交流障碍患儿遗传学病因，并对其临床表型进行遗传学分析。 方法 采用患儿及其父母外周血进行常规G显带染色体核型分析及单核苷酸多态性微阵列(single nucleotide polymorphism array，SNP array)检测。 结果 患儿染色体核型为47，XY，＋mar[44]/46，XX[20]，SNP array检测结果显示患儿约65%的细胞在15q11.2-q14区段存在11.5 Mb(22，770，421-34，671，762)片段的嵌合重复，该区域涉及5个断裂点(break point，BP)的3个区间：BP1-BP2(15q11.2)区间重复；BP2-BP3(15q11.2-q13.1)经典重复区间Prader Willi综合征(Prader Willi syndrome，PWS)/Angelman综合征(Angelman syndrome，AS)区间重复；远端的BP4-BP5(15q13.2-q13.3)重复。父母染色体核型分析未见异常，SNP array在全染色体基因组范围内未检测到染色体片段拷贝数的异常变化。 结论 患儿15q11.2-q14发生的嵌合重复性额外小标记染色体(small supernumerary marker chromosomes，sSMCs)为新发突变。该患儿的临床表型与15q11.2-q14区段的重复涉及的基因相关，可为遗传咨询提供帮助。 Objective To clarify the genetic cause of a child with mental retardation, abnormal development and language communication disorder, and to make genetic analysis on its clinical phenotype. Methods Routine G-banding karyotype analysis and single nucleotide polymorphism array (SNP array) were performed in peripheral blood of children and their parents. Results The karyotype of the child was 47, XY, + mar[44]/46, XX[20], the results of SNP array showed that about 65% of the cells in children had 11.5 Mb (22, 770, 421-34, 671, 762) in the 15q11.2-q14 segment. Chimeric duplication of fragments, which involves three intervals of five break point (BP): BP1-BP2(15q11.2) interval duplication BP2-BP3(15q11.2-q13.1) The classical repetition interval is repeated in the interval of Prader Willi syndrome (PWS)/Angelman syndrome (AS) The remote BP4-BP5(15q13.2-q13.3) is duplicated. There was no abnormality in the karyotype analysis of parents, and SNP array did not detect any abnormal change in the copy number of chromosome fragments within the whole chromosome genome. Conclusion The chimeric repetitive small supernumerary marker chromosomes (sSMCs) in children with 15q11.2-q14 are new mutations. The clinical phenotype of this child is related to the gene involved in the 15q11.2-q14 segment duplication, which can provide help for genetic counseling.

    额外标记染色体嵌合核型分析单核苷酸多态性

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    PKD1基因变异致多囊肾病家系1例的临床与遗传学分析

    刘庄王钦张敏魏泽锋...
    55-62页
    查看更多>>摘要：目的 探讨1个常染色体显性多囊肾病(autosomal dominant polycystic kidney disease，ADPKD)家系PKD1基因变异的致病性，并进行遗传咨询和再生育指导。 方法 采集家系成员及100名健康对照者外周血，通过全外显子测序法筛选先证者全外显子组变异基因；应用PCR及Sanger测序验证先证者及其家系成员候选变异基因位点，并进一步筛查健康对照者；结合先证者家系的临床信息及ACMG/AMP指南进行新变异的致病性解读，应用ExAC、dbSNP、HGMD、千人基因组、ClinVar、PKDB、Mutation Taster和Uniprot数据库及软件进行突变人群频率和生物信息学分析。 结果 超声检查显示先证者双肾多发囊性回声；全外显子测序结果显示先证者及其女儿、父亲、姑姑、姑表妹均存在PKD1 c.4076T>C(p.Leu1359Pro)杂合错义变异，且100名健康对照者中均未发现该变异。本家系中的多囊肾患者存在PKD1 c.4076T>C(p.Leu1359Pro)杂合错义变异，根据ACMG/AMP指南，该变异分类为可能致病性(PS4_Supporting＋PP1_Moderate＋PM2_Supporting＋PP3＋PP4)。 结论 PKD1基因c.4076T>C(p.Leu1359Pro)杂合错义变异的发现丰富了PKD1基因的变异谱，为该家系的遗传咨询和遗传学诊断提供了依据，避免了再生育发病的风险。 Objective To investigate the pathogenic of PKD1 gene mutation in an autosomal dominant polycystic kidney disease ( ADPKD ) family, and to provide genetic counseling and reproductive guidance. Methods Peripheral blood samples were collected from family members and 100 healthy controls, and the whole exome mutation genes of the proband were screened by the whole exome sequencing. PCR and Sanger sequencing were used to verify the candidate mutation gene loci of the proband and his family members, and further screen healthy controls. Combined with the clinical information of the proband’s family and the ACMG / AMP guidelines, the pathogenic interpretation of the new mutation was performed using ExAC, dbSNP, HGMD, 1000 genomes project, ClinVar, PKDB, Mutation Taster and Uniprot databases and software were used to analyze the mutation population frequency and the analysis of bioinformatics. Results Ultrasound examination showed multiple cystic echoes in both kidneys of the proband high-throughput sequencing results showed that the proband and his daughter, father, aunt and cousin all had heterozygous missense mutation of PKD1 gene c. 4076T>C ( p. Leu1359Pro ), and this mutation was not found in 100 healthy controls.PKD1 gene c. 4076T>C (p.Leu1359Pro) heterozygous missense mutation was found in the polycystic kidney patients in this family. According to the ACMG/AMP guidelines, the mutation was classified as likely pathogenic(PS4_ Supporting+ PP1_Moderate+ PM2_Supporting+ PP3+ PP4). Conclusion The discovery of heterozygous missense mutation of PKD1 gene c. 4076T>C ( p. Leu1359Pro ) enriches the mutation spectrum ofPKD1 gene, provides a basis for genetic counseling and genetic diagnosis of the family, and avoids the risk of re-fertility.

    常染色体显性多囊肾病(ADPKD)全外显子测序PKD1基因新变异

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    TBR1基因的新发移码突变导致患儿智力障碍伴自闭症1例

    姜园园薛涛李雪候丹妮...
    63-67页
    查看更多>>摘要：目的 探讨1例智力发育障碍伴自闭症和语言障碍(intellectual developmental disorder with autism and speech delay，IDDAS)患儿的临床特征与基因突变情况。 方法 回顾分析1例IDDAS患儿的临床资料，应用全外显子测序对患儿及家系进行基因变异情况检测，进行致病性分析。 结果 患儿存在轻度的智力发育落后、脑损伤，并有情绪障碍、学习习惯异常及自闭倾向。相对于既往报道的IDDAS患者表型，本案例患儿存在性早熟(乳房早发育)的新表型；基因检测结果显示患儿TBR1基因存在c.874dup(p.Ser292Phefs*29)杂合移码突变，父母为野生型，即患儿的变异为新发变异。ACMG评级为致病，且此前尚未见文献报道及数据库收录，为新发现的致病性突变。 结论 TBR1基因的c.874dup(p.Ser292Phefs * 29)杂合移码突变为该患儿的致病性突变，本案例的报道丰富了IDDAS的临床表型和基因突变谱，可为后续类似患者的临床诊断提供可参考依据。 Objective To explore the clinical characteristics and gene mutations of a child with intellectual developmental disorder with autism and speech delay (IDDAS). Methods Retrospective analysis of the clinical data of a child with IDDAS, using whole exome sequencing to detect gene mutations in the patient and family, and conducting pathogenic analysis. Results The child who suffers mild mental retardation, brain damage, emotional disturbances, abnormal learning habits and autism. Compared with reported patients, the patient in this paper showed a new phenotype of puberty as praecox (Premature thelarche). Genetic tests showed that the child had a c. 874dup(p.Ser292Phefs * 29) heterozygous frameshift variant in the TBR1 gene, which was rated as pathogenic by ACMG. The proband’s parents did not have this variant, which meant the child had a de novo mutation. Furthermore, the variant had not been previously reported in the literature or included in databases, showing that this variant is a newly discovered mutation. Conclusion The c. 874dup (p.Ser292Phefs * 29) heterozygous frameshift mutation in the TBR1 gene is a candidate pathogenic mutation for this patient. The report of this case enriches the clinical phenotype and gene mutation spectrum of IDDAS, providing a reference basis for subsequent clinical diagnosis of similar patients.

    自闭症TBR1基因高通量测序智力发育障碍

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    HECW2基因变异致神经发育迟滞1例的遗传学分析

    陈雪马盼盼田芯瑗郑雷...
    68-73页
    查看更多>>摘要：目的 探讨1例神经发育迟滞患儿的分子遗传学病因。 方法 选取2022年5月9日因"发育迟滞、营养不良"就诊于甘肃省妇幼保健院的1例年龄为8月的女性患儿作为研究对象。收集患儿的临床资料，提取患儿及其父母的外周血样DNA，进行全外显子组测序(whole exome sequence，WES)，用Sanger测序对候选变异进行家系验证。 结果 经trio-WES数据分析，筛选到与患儿临床表型相关的HECW2基因c.4505G>C(p.Gly1502Ala)变异，Sanger测序的结果与trio-WES一致，经双亲验证证实为新发变异。根据美国医学遗传学与基因组学(American College of Medical Genetics and Genomics，ACMG)指南对变异位点c.4505G>C(p.Gly1502Ala)进行致病性评估为可能致病性变异(PS2＋PM2_Supporting＋PP2＋PP3_Moderate)。 结论 本研究患儿HECW2基因c.4505G>C(p.Gly1502Ala)杂合变异尚未报道，该发现为患者明确诊断提供了依据，且扩展了其致病变异谱，对患儿的确诊、遗传咨询及其父母的再生育指导具有重要的意义。 Objective To analyze the molecular genetic etiology of a patient with neurodevelopmental delay. Methods A 8-month-old female child who was admitted to Gansu Provincial Maternity and Child HealthCare Hospital on May 9, 2022 due to developmental delay and malnutrition was selected as the study subject.Clinical data of the child was collected, and genomic DNA was extracted from peripheral blood samples from the child and her parents. Whole exome sequencing(WES)was carried out, and candidate variants were verified by Sanger sequencing. Results After analyzing the data from trio WES, a variant of the HECW2 gene c. 4505G>C (p.Gly1502Ala) was identified that is related to the clinical phenotype of the patient. The results of Sanger sequencing were consistent with trio WES, and confirmed as a novel variant through parental verification. Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG), the c. 4505G>C(p.Gly1502Ala) variant was graded as likely pathogenic(PS2+ PM2_Supporting+ PP2+ PP3_Moderate). Conclusion The heterozygous variation of the HECW2 gene c. 4505G>C(p.Gly1502Ala) in this study is an unreported mutation.Our findings not only provide a clear diagnosis for this patient, but also expand their pathogenic spectrum. Above finding has facilitated definite diagnosis, genetic counseling for her family.

    神经发育迟滞HECW2基因全外显子测序基因变异

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