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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。
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    非单纯性睑-唇-齿综合征一个家系的遗传学分析

    闫露露刘颖文张玉鑫田丽蕴...
    36-41页
    查看更多>>摘要：目的 探讨1个非单纯性睑-唇-齿综合征(BCDS)家系的遗传学病因。 方法 选取2020年9月28日于宁波市妇女儿童医院就诊的1个BCDS家系为研究对象。通过全外显子组测序对胎儿及其父母和哥哥进行基因与拷贝数变异(CNVs)分析，用Sanger测序和实时荧光定量PCR(qPCR)分别对结果进行验证。 结果 胎儿及其哥哥、父亲、祖父均携带CTNND1基因c.83delG(p.A29Rfs*55)杂合变异，既往未见报道。此外，胎儿的哥哥还携带母源性GJB2基因c.235delC(p.L79Cfs*3)和父源性GJB3基因c.538C>T(p.R180X)双杂合变异；CNVs分析发现母亲17q12区存在1.46 Mb缺失，涉及HNF1B、ZNHIT3等16个OMIM基因，对胎儿的外祖父母进行qPCR验证，证实为新发变异。根据美国医学遗传学和基因组学学会相关指南，c.83delG及c.235delC均评判为致病性变异(PVS1+PP1_Moderate+PM2_Supporting，PVS1+PM3_VeryStrong+PS3_Moderate)；c.538C>T评判为意义不明变异(PS3+PM2_Supporting)；17q12微缺失评判为致病性(pathogenic，total score：1.0)。 结论 CTNND1基因c.83delG(p.A29Rfs*55)变异可能是该非单纯性BCDS家系的遗传学病因。GJB2基因c.235delC和GJB3基因c.538C>T变异可能为哥哥耳聋的致病原因。17q12微缺失可能为母亲双肾囊肿的致病原因。上述发现为该家系的遗传咨询和再生育提供了指导。 Objective To explore the genetic etiology of a Chinese pedigree featuring non-simplex blepharocheilodontic syndrome. Methods Whole exome sequencing was carried out to detect genetic variant and copy number variations (CNVs) in the pedigree. Suspected variants were verified by Sanger sequencing and qPCR. Results The fetus and its elder brother, father and grandfather were found to harbor a heterozygous c. 83delG (p.A29Rfs*55) variant of the CTNND1 gene, which was unreported previously. In addition, its elder brother was also found to be a double heterozygote for a c. 235delC(p.L79Cfs*3) variant of GJB2 gene and a c. 538C>T (p.R180X) variant ofGJB3 gene, which were respectively inherited from his mother and father. CNVs analysis revealed a de novo heterozygotic deletion (1.46 Mb) at 17q12 in the mother, which was confirmed by qPCR. Based on American College of Medical Genetics and Genomics guidelines, the c. 83delG variant, the c. 235delC variant and the 17q12 microdeletion were predicted as pathogenic, while the c. 538C>T variant was of uncertain significance. Conclusion The c. 83delG (p.A29Rfs*55) variant of the CTNND1 gene probably underlay the pathogenesis of non-simplex blepharocheilodontic syndrome in this pedigree. The double heterozygous variants of c. 235delC (p.L79Cfs*3) of GJB2 gene and c. 538C>T (p.R180X) ofGJB3 gene probably underlay the hearing loss in the elder brother. The bilateral renal cysts in the mother may be attributed to the 17q12 microdeletion. Above results have provided guidance for genetic counseling and prenatal diagnosis for this pedigree.

    睑-唇-齿综合征CTNND1基因全外显子组测序17q12缺失综合征

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    BCL11A相关智力障碍一个家系的遗传学分析

    刘爱玲胡艳艳崇保强郑书琪...
    42-46页
    查看更多>>摘要：目的 探讨1家系中2例BCL11A相关智力障碍(BCL11A-ID)患者的遗传学病因。 方法 选取2020年6月19日，于临沂市人民医院遗传咨询门诊就诊的1个BCL11A-ID家系为研究对象。分析先证者及家系成员的临床资料，并进行染色体核型分析、家系全外显子组测序(trio-WES)、拷贝数变异测序(CNV-seq)，可疑变异经Sanger测序验证并进行致病性评估。 结果 先证者及其母亲表现为智力障碍及语言发育迟缓，二者的胎儿血红蛋白(HbF)显著升高。WES发现先证者BCL11A基因第4外显子存在c.1327_c.1328delTC(p.Ser443Hisfs*128)杂合变异，导致编码蛋白截短表达，Sanger测序验证该变异遗传自母亲。检索相关数据库未见报道，为新变异。根据美国医学遗传学与基因组学学会(ACMG)指南判定为致病性变异(PVS1+PM2+PP1)。先证者及其父母、哥哥的染色体核型分析未见异常，先证者及其父母的CNV-seq未见异常。 结论 本研究确诊了先证者及其母亲为BCL11A-ID患者，c.1327_c.1328delTC(p.Ser443Hisfs*128)变异可能是该病的致病原因，丰富了BCL11A基因的变异谱。 Objective To explore the genetic basis for two patients from a family with BCL11A-related intellectual disability (BCL11A-ID). Methods Clinical data of the proband and her family members was analyzed. Chromosomal karyotyping analysis, trio-whole exome sequencing (trio-WES) and copy number variation sequencing (CNV-seq) were carried out. For the suspected genetic variants, Sanger sequencing was used to verify, and pathogenicity assessment was conducted. Results The proband and her mother both had intellectual and language impairment, and their fetal hemoglobin (HbF) was significantly elevated. A heterozygous c. 1327_c.1328delTC (p.Ser443Hisfs*128) variant was found in exon 4 of the BCL11A gene by WES, which has resulted in truncated expression of the encoded protein, and Sanger sequencing has verified that the variant was inherited from the mother. The variant was not found in related databases. The variant was predicted as a pathogenic variant according to the guidelines from the American College of Medical Genetics and Genomics (ACMG) (PVS1+ PM2+ PP1). No karyotypic abnormality was found in the proband, her parents and brother, and no pathogenic CNVs were found in the proband and her parents. Conclusion The c. 1327_c.1328delTC (p.Ser443Hisfs*128) variant may underlay the BCL11A-ID in the proband and her mother. This de novo variant has expanded the mutational spectrum of the BCL11A gene.

    BCL11A基因智力障碍语言发育迟缓新变异

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    CHAMP1基因变异所致常染色体显性智力障碍40型患儿1例的分析

    徐菁晗李晶晶焦智慧孙阁阁...
    47-52页
    查看更多>>摘要：目的 探讨1例CHAMP1基因变异所致常染色体显性智力障碍40型(MRD40)患儿的临床表型和遗传学特征。 方法 选取2019年10月至2020年9月于郑州大学第一附属医院就诊的1例MRD40型患儿为研究对象。采集患儿的临床资料，用低深度高通量全基因组拷贝数变异测序(CNV-seq)和全外显子组测序(WES)对其进行遗传学分析，并回顾文献报道的CHAMP1基因变异所致MRD40病例的临床表型和遗传学特征。 结果 患儿，女，11月龄，表现为全面发育迟缓合并特殊面容。CNV-seq检测未见异常，WES结果提示其携带CHAMP1基因c.1908C>G(p.Y636*)新发杂合变异。连同12篇文献报道的33例患儿，除发育迟缓、智力障碍外，大多存在肌张力减退(94.1%)、说话和/或行走时间延迟(85.2%，82.4%)及眼部异常(79.4%)。共检出CHAMP1基因变异26个，大多为功能缺失变异，位于第3外显子且为新发。 结论 CHAMP1基因c.1908C>G(p.Y636*)杂合变异可能是本例患儿的致病原因。对于全面发育迟缓/智力障碍、肌张力减退伴特殊面容的患儿，应尽早进行基因检测以明确病因。 Objective To explore the clinical and genetic features of a child with autosomal dominant mental retardation type 40 (MRD40) due to variant of the CHAMP1 gene. Methods Clinical characteristics of the child were analyzed. Genetic testing was carried out by low-depth high-throughput and whole genome copy number variant sequencing (CNV-seq) and whole exome sequencing (WES). A literature review was also carried out for the clinical phenotype and genetic characteristics of patients with MRD40 due to CHAMP1 gene variants. Results The child, a 11-month-old girl, has presented with intellectual and motor developmental delay. CNV-seq revealed no definite pathogenic variants. WES has detected the presence of a heterozygous c. 1908C>G (p.Y636*) variant in theCHAMP1 gene, which was carried by neither parent and predicted to be pathogenic. Literature review has identified 33 additional children from 12 previous reports. All children had presented with developmental delay and mental retardation, and most had dystonia (94.1%), delayed speech and/or walking (85.2%, 82.4%), and ocular abnormalities (79.4%). In total 26 variants of the CHAMP1 gene were detected, with all nonsense variants being of loss-of-function type, located in exon 3, and de novo in origin. Conclusion The heterozygous c. 1908C>G (p.Y636*) variant of theCHAMP1 gene probably underlay the WRD40 in this child. Genetic testing should be considered for children featuring global developmental delay, mental retardation, hypertonia and facial dysmorphism.

    常染色体显性智力障碍40型CHAMP1基因发育迟缓全外显子组测序

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    Schaaf-Yang综合征患儿1例的临床与遗传学分析

    罗娟陈晓红姚辉杨禄红...
    53-56页
    查看更多>>摘要：目的 探讨1例Schaaf-Yang综合征(SYS)患儿的临床特征与遗传学病因。 方法 选取2020年11月30日于华中科技大学同济医学院附属武汉儿童医院就诊的1例SYS患儿为研究对象。抽取患儿及其父母外周静脉血样，应用全外显子组测序对患儿进行基因检测，采用Sanger测序进行家系验证，并对候选变异进行生物信息学分析。 结果 ①本例患儿为男性，1岁9个月，具有发育迟滞、阴茎短小、特殊面容等临床表现。②基因检测结果提示，患儿MAGEL2基因存在c.3078dupG(p.Leu1027Valfs*28)新发杂合变异，Sanger测序结果显示患儿父母均未携带该变异，提示为新发变异。③MAGEL2基因c.3078dupG(p.Leu1027Valfs*28)变异在ESP、1000 Genomes与ExAC等数据库中均未见收载，根据美国医学遗传学与基因组学学会(ACMG)制定的《ACMG遗传变异分类标准与指南》，该变异被评级为致病性变异。 结论 MAGEL2基因c.3078dupG(p.Leu1027Valfs*28)变异可能为本例SYS患儿的遗传学病因，进一步拓展了MAGEL2基因变异谱。 Objective To explore the clinical characteristics and genetic etiology of a child with Schaaf-Yang syndrome (SYS). Methods Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing. Sanger sequencing was used for family constellation verification, and bioinformatic analysis was performed for the candidate variant. Results The child, a 1-year-and-9-month-old boy, had clinical manifestations of retarded growth, small penis, and unusual facies. Genetic testing revealed that the child has harbored a novel heterozygous variant of c. 3078dupG (p.Leu1027Valfs*28) of the MAGEL2 gene. Sanger sequencing showed that neither parent of the child carried the same variant. The c. 3078dupG(p.Leu1027Valfs*28) variant of the MAGEL2 gene has not been included in the databases of ESP, 1000 Genomes and ExAC. According to the Standards and Guidelines for the Interpretation of Sequence Variants of the American College of Medical Genetics and Genomics (ACMG), the variant was judged to be pathogenic. Conclusion The c. 3078dupG (p.Leu1027Valfs*28) variant of the MAGEL2 gene probably underlay the SYS in this child, which has further expanded the spectrum of the MAGEL2 gene variants.

    Schaaf-Yang综合征MAGEL2基因移码变异基因变异

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    SYNGAP1基因移码变异所致精神发育迟滞患儿1例的遗传学分析

    沈玥罗冠君陆超谭媛...
    57-61页
    查看更多>>摘要：目的 探讨1例精神发育迟滞患儿的遗传学病因。 方法 选取2020年8月6日于广州中医药大学附属南海妇产儿童医院就诊的1例精神发育迟泄患儿为研究对象。用全外显子组测序技术对患儿及其父母进行变异筛查，结合临床资料分析可能的致病变异，并通过Sanger测序进行验证。 结果 基因测序提示患儿携带SYNGAP1基因杂合移码变异c.995_1002delAGACAAAA(p.Asp332AlafsTer84)，其父母未携带相同变异。 结论 SYNGAP1基因c.995_1002delAGACAAAA(p.Asp332AlafsTer84)移码变异可能是患儿精神发育迟滞的遗传学原因。上述发现丰富了SYNGAP1基因的变异谱，为患儿的诊断和治疗提供了依据。 Objective To explore the genetic basis for a child with mental retardation. Methods Whole exome sequencing was carried out for the child. Candidate variant was screened based on his clinical features and verified by Sanger sequencing. Results The child was found to harbor a c. 995_1002delAGACAAAA(p.Asp332AlafsTer84) frameshift variant in the SYNGAP1 gene. Bioinformatic analysis suggested it to be pathogenic. The same variant was not detected in either parent. Conclusion The c. 995_1002delAGACAAAA(p.Asp332AlafsTer84) frameshift variant of the SYNGAP1 gene probably underlay the mental retardation in this child. Above finding has expanded the spectrum of SYNGAP1 gene variants, and provided a basis for the diagnosis, treatment for this child.

    精神发育迟滞SYNGAP1基因移码变异

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    FBN1基因新变异所致马凡综合征患儿1例的分析

    赵立玲刘升平胡文沐金萍...
    62-65页
    查看更多>>摘要：目的 探讨1例马凡综合征(MFS)患儿的遗传学病因，并分析其临床表型与基因型的相关性。 方法 选取2021年3月30日于中南大学湘雅三医院就诊的1例MFS患儿为研究对象。收集患儿及其家系成员的外周血样，提取基因组DNA，进行家系全外显子组测序，对候选致病变异进行Sanger测序家系验证，并用生物信息学软件分析变异的致病性。 结果 患儿为13岁男性，MFS体型包括身材瘦长、臂展大于身高、手指及足趾细长、漏斗胸、脊柱侧弯，但未见主动脉扩张或胸腹主动脉瘤、二尖瓣脱垂等典型病变，晶状体未见脱位。全外显子组测序显示其FBN1基因存在c.7383_7413del(p.N2461Kfs*211)杂合变异，其父母、弟弟均未发现相同的变异。该变异既往未见文献报道，被判断为致病性。 结论 本研究发现了FBN1基因的一个新变异，进一步拓展了MFS的变异谱及表型谱。 Objective To carry out genetic testing for a child with Marfan syndrome (MFS) and explore its genotype-phenotype correlation. Methods Peripheral blood samples of the child and his parents were collected for the extraction of genomic DNA and subjected to whole exome sequencing(WES). Candidate variants were verified by Sanger sequencing. Functional impact of the variant was predicted by using bioinformatic software. Results The child, a 13-year-old male, has featured Marfanoid habitus, with arm span exceeding his height, tapering fingers and toes, pectus excavatum and scoliosis, but absence of typical cardiovascular system diseases such as aortic dilation, thoracic-abdominal aortic aneurysm, mitral valve prolapse, and lens dislocation. The child has harbored a novel splice site variant c. 7383_7413del (p. N2461Kfs*211) of the FBN1 gene, which was not found in his parents and younger brother. The variant was unreported previously. Conclusion The novel variant of p. N2461Kfs*211 of the FBN1 gene probably underlay the MFS in this child. Above finding has enriched the genotypic and phenotypic spectrum of MFS.

    马凡综合征FBN1基因新变异

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    胰岛素基因新变异所致永久性新生儿糖尿病患儿1例的临床及遗传学分析

    李玛丽李佳邱世超宋娜...
    66-70页
    查看更多>>摘要：目的 分析1例永久性新生儿糖尿病(PNDM)患儿的临床及遗传学特征。 方法 选取2019年8月于西安市儿童医院就诊的1例PNDM患儿为研究对象。收集患儿的临床资料及实验室检查结果，应用靶向捕获高通量测序进行变异位点分析，针对筛选出的候选靶基因用Sanger测序进行家系验证。 结果 患儿系4个月26天女婴，以酮症酸中毒起病，空腹血糖24.4 mmol/L，尿糖阳性，血清C肽降低，糖化血红蛋白9.58%，糖尿病自身抗体阴性。基因检测发现患儿胰岛素INS基因存在c.314T>G(p.L105R)杂合变异。Sanger测序证实患儿父母均未携带上述变异，为新发变异。该变异尚未见文献及数据库报道，根据美国医学遗传学与基因组学学会指南，评级为疑似致病变异。 结论 INS基因c.314T>G(p.L105R)变异可能是该患儿的遗传学病因。对于临床疑似PNDM的患儿建议早期行基因检测。 Objective To explore the genetic basis for an infant with permanent neonatal diabetes mellitus (PNDM). Methods Clinical data of the child was collected. Targeted capture-next generation sequencing was carried out to identify the potential variants. Candidate variant was verified by Sanger sequencing of her family members. Results The child was a 4-month-and-26-day female featuring onset of ketoacidosis accompanied with fasting blood glucose of 24.4 mmol/L, positive urine glucose, decreased serum C-peptide, HbA1c of 9.58%, and negative diabetes autoantibody. Genetic testing revealed that she has carried a heterozygous c. 314T>G (p.L105R) variant of theINS gene. Sanger sequencing verified that neither of her parents has carried the same variant, which was also unreported in the literature. The variant was classified as likely pathogenic based on the ACMG guidelines. Conclusion The c. 314T>G (P.L105R) variant of theINS gene probably underlay the genetic etiology in this child. Genetic testing should be conducted for children with suspected PNDM for early diagnosis and appropriate treatment.

    永久性新生儿糖尿病INS基因酮症酸中毒基因变异

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    DNAH5基因新型复合杂合变异所致Kartagener综合征患儿1例的临床及遗传学分析

    张珊王朝兵张勇胡言东...
    71-75页
    查看更多>>摘要：目的 分析1例Kartagener综合征(KTS)患儿的临床特征与遗传学病因。 方法 选取2020年10月于邛崃市妇幼保健院就诊的1例KTS患儿为研究对象。对患儿及其父母进行家系全外显子组测序以及生物信息学分析，通过Sanger测序进一步验证候选变异。模拟分析错义变异导致的蛋白结构改变，应用HSF 3.0在线平台对非编码区变异进行危害性预测。 结果 患儿具有支气管扩张、鼻窦炎及内脏反位等临床表现，基因检测提示其DNAH5基因存在c.5174T>C与c.7610-3T>G复合杂合变异，Sanger测序证实二者分别遗传自患儿母亲和父亲。两个变异在dbSNP、1000 Genomes、ExAC、ClinVar及HGMD等数据库中均未见收录。蛋白结构分析结果提示c.5174T>C(p.Leu1725Pro)可能影响蛋白局部结构的稳定性从而影响生物活性，HSF 3.0分析结果提示c.7610-3T>G可能破坏剪接受体从而影响转录。 结论 DNAH5基因c.5174T>C与c.7610-3T>G复合杂合变异可能是患儿的遗传学病因。上述发现进一步拓展了DNAH5基因的变异谱。 Objective To explore the clinical characteristics and genetic basis of a child with Kartagener syndrome (KTS). Methods Trio-whole exome sequencing was carried out for the child and his parents, and candidate variants were verified by Sanger sequencing. Changes in protein structure due to missense variants were simulated and analyzed, and the Human Splicing Finder 3.0 (HSF 3.0) online platform was used to predict the effect of the variant of the non-coding region. Results The child had featured bronchiectasis, sinusitis and visceral inversion. Genetic testing revealed that he has harbored compound heterozygous variants of the DNAH5 gene, namely c. 5174T>C and c. 7610-3T>G. Sanger sequencing confirmed the existence of the variants. The variants were not found in the dbSNP, 1000 Genomes, ExAC, ClinVar and HGMD databases. Protein structural analysis suggested that the c. 5174T>C (p.Leu1725Pro) variant may affect the stability of local structure and its biological activity. The results of HSF 3.0 analysis suggested that the c. 7610-3T>G variant has probably destroyed a splicing receptor to affect the transcription process. Conclusion The compound heterozygous variants of the DNAH5 gene probably underlay the pathogenesis in the child. Above finding may facilitate the understanding of the clinical characteristics and genetic basis of KTS, and further expand the spectrum DNAH5 gene variants.

    原发性纤毛运动障碍Kartagener综合征DNAH5基因非编码区变异

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    ITPR1基因新发变异所致脊髓小脑性共济失调29型患儿1例的诊断

    智亚楠刘娇甄诚李娟...
    76-80页
    查看更多>>摘要：目的 分析1例ITPR1基因新发变异所致脊髓小脑性共济失调29型(SCA29)患儿的临床特征和遗传学特点。 方法 选取2020年7月1日于河北省人民医院就诊的1例SCA29患儿为研究对象。对患儿进行高通量测序，通过Sanger测序对候选变异进行家系验证。 结果 高通量测序显示患儿携带ITPR1基因c.800C>T(p.T267M)杂合变异，胎儿及父母Sanger测序均未检测到此变异，此新发变异既往国内未见报道，且位于ITPR1基因的变异热点区域，结合患儿的临床表型，诊断其为SCA29。 结论 ITPR1基因c.800C>T(p.T267M)位点杂合变异可能是本例SCA29患儿的重要致病原因。 Objective To explore the clinical and genetic characteristics of a child with spinocerebellar ataxia type 29 (SCA29)due to novel variant of the inositol 1, 4, 5-trisphosphate receptor type 1 (ITPR1) gene. Methods The child was subjected high-throughput sequencing, and candidate variant was verified by Sanger sequencing of his family members. Results The child was found to harbor a c. 800C>T (p.T267M) variant of theITPR1 gene, which was not found in his parents and their fetus. The variant has occurred in a hotspot of the ITPR1 gene variants and was unreported before in China. Based on his clinical and genetic characteristics, the child was diagnosed with SCA29. Conclusion The novel heterozygous c. 800C>T (p.T267M) of theITPR1 gene probably underlay the SCA29 in this child.

    脊髓小脑性共济失调Ⅰ型1,4,5-三磷酸肌醇受体基因变异

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    RNASEH2C基因复合杂合变异所致艾卡迪综合征3型患儿1例的临床及遗传学分析

    刘娟胡继红覃蓉段雅琴...
    81-86页
    查看更多>>摘要：目的 探讨1例RNASEH2C基因变异所致Aicardi-Goutières综合征3型(AGS 3)患儿的临床特征与遗传学病因。 方法 选取2021年3月27日于湖南省儿童医院就诊的1例AGS3患儿为研究对象。对患儿及其父母进行家系全外显子组测序，并利用Sanger测序对候选变异进行验证。对变异进行晶体结构模拟分析，并构建质粒进行蛋白表达。通过检索文献，总结AGS 3型的表型与遗传学特点。 结果 患儿RNASEH2C基因存在复合杂合变异c.494G>C(p.Ter165Ser)(父源)与c.434G>T(p.Arg145Leu)(母源)，既往均未见报道。蛋白结构预测分析c.434G>T(p.Arg145Leu)变异可能破坏局部结构的稳定性，体外功能实验表明该变异将导致蛋白表达降低。c.494G>C(p.Ter165Ser)变异破坏了终止密码子，导致蛋白产物延长。 结论 本研究发现了两个RNASEH2C基因的新变异，进一步丰富了AGS 3型的表型与变异谱。 Objective To explore the clinical characteristics and genetic etiology of a child with Aicardi-Goutières syndrome 3 (AGS3). Methods Trio whole exome sequencing was carried out for the child and his parents, and candidate variants were verified by Sanger sequencing. To further clarify their pathogenicity, the crystal structure of the variants was simulated and analyzed, and the plasmid of variants was expressed in vitro. A literature search was also carried out to summarize the phenotypic and genetic characteristics of AGS3. Results The child was found to harbor novel compound heterozygous variants of the RNASEH2C gene, namely c. 434G>T (p.Arg145Leu) and c. 494G>C (p.Ter165Ser), which were inherited from his mother and father, respectively. Analysis of protein crystal structure suggested that the c. 434G>T (p.Arg145Leu) variant may affect the stability of local structure, andin vitro experiments showed that this variant can lead to protein degradation. The c. 494G>C (p.Ter165Ser) variant has destroyed the stop codon, resulting in prolonged variant. Conclusion The novel compound heterozygous variants of the RNASEH2C gene probably underlay the AGS3 in this child, which has enriched the phenotypic and mutational spectrum of this disorder.

    Aicardi-Goutières综合征3型RNASEH2C基因终止密码子新变异

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