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

    ANKRD11基因新变异所致KBG综合征患儿3例的临床及遗传学分析

    王莉李晶晶徐菁晗徐彦磊...
    1-6页
    查看更多>>摘要：目的 探讨3例KBG综合征患儿的临床与遗传学特征。 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3例KBG患儿为研究对象。收集2个家系3例患儿及其家系成员的临床资料，并进行家系全外显子组测序(trio-WES)和Sanger测序。 结果 3例患儿均有喂养困难、先天性心脏缺陷和特殊面容等表现。家系1中的2例患儿均检出ANKRD11基因c.6270delT(p.Q2091Rfs*84)新发杂合变异；家系2中的1例患儿检出ANKRD11基因c.6858delC(p.D2286Efs*51)新发杂合变异，遗传自具有轻微临床表型的母亲。 结论 ANKRD11基因移码变异可能是3例KBG综合征患儿的遗传学病因。上述发现丰富了ANKRD11基因的变异谱。 Objective To explore the clinical and genetic characteristics of three children with KBG syndrome. Methods Clinical data of the three children from two families who have presented at the First Affiliated Hospital of Zhengzhou University between October 2019 and September 2020 and their family members were collected. Trio-whole exome sequencing (trio-WES) and Sanger sequencing were carried out. Results All children had feeding difficulties, congenital heart defects and facial dysmorphism. The sib pair from family 1 was found to harbor a novel de novo heterozygous c. 6270delT (p.Q2091Rfs*84) variant of the ANKRD11 gene, whilst the child from family 2 was found to harbor a novel heterozygous c. 6858delC (p.D2286Efs*51) variant of the ANKRD11 gene which was inherited from his mother who had a mild clinical phenotype. Conclusion The heterozygous frameshift variants of the ANKRD11 gene probably underlay the disease in the three children. Above findings have enriched the spectrum of the ANKRD11 gene variants.

    KBG综合征ANKRD11基因家系全外显子组测序新变异

      原文链接:
    • 万方数据

    t(2；18)(q36；q23)致反复流产及胎儿异常1例

    孙诗雨蓝信强李岭
    6页
    查看更多>>摘要：孕妇 36岁，G 7P 0，前4次妊娠均于孕早期自然流产，其中第4次流产物行绒毛染色体分析，核型为46，XX，der(18)t(18；？)(q23；？)(图1)。第5次妊娠孕中期B超示胎儿主动脉骑跨、肺动脉狭窄、房室间隔缺损，考虑为法洛四联征，选择引产。第6次妊娠孕中期B超提示胎儿右手缺失，双侧脑室为正常值上限，三尖瓣少量返流，引产后发现胎儿左脚内翻。本次妊娠孕中期B超再次提示胎儿双侧足内翻，在签署知情同意书后行羊水穿刺产前诊断。否认近亲结婚、孕期有害物质及放射线接触史。本研究通过本院医学伦理委员会的审查(WHFY-YXLLWYH-L2022011)。
      原文链接:
    • 万方数据

    Cornelia de Lange综合征患儿3例的基因型及表型分析

    赵磊张庆华周秉博张钏...
    7-11页
    查看更多>>摘要：目的 对3例Cornelia de Lange综合征(CdLS)患儿的临床表型及基因检测结果进行分析，明确其致病原因。 方法 选取2020年3月12日、8月14日、12月5日于甘肃省妇幼保健院医学遗传中心就诊的3例CdLS患儿为研究对象。收集患儿及其父母的临床资料，采集外周血样进行家系高通量测序分析。 结果 3例患儿的主要临床表现包括发育迟缓、智力低下、特殊面容和其他伴随症状。根据国际诊断共识标准，3例患儿被拟诊为CdLS。通过家系全外显子组测序及生物信息学分析，确诊CdLS。患儿1携带NIPBL基因c.5567_5569delGAAinsTAT错义变异，患儿2携带SMC1A基因c.607A>G错义变异，患儿3携带HDAC8基因c.628+1G>A剪接变异。3例患儿均为新发变异。 结论 3例患儿均确诊CdLS，并发现了致病基因变异位点，其中NIPBL基因c.5567_5569delGAAinsTAT及HDAC8基因c.628+1G>A变异位点既往未见报道，丰富了CdLS的变异谱。 Objective To analyze the clinical phenotype and results of genetic testing in 3 children with Cornelia de Lange syndrome (CdLS). Methods Clinical data of the children and their parents were collected. Peripheral blood samples of the pedigrees were collected for next generation sequencing analysis. Results The main clinical manifestations of the 3 children have included growth delay, mental retardation, peculiar facies and other accompanying symptoms. Based on the criteria proposed by the International Diagnostic Consensus, all 3 children were suspected for CdLS. As revealed by whole exome sequencing, child 1 has harbored NIPBL gene c. 5567_5569delGAA insTAT missense variant, child 2 has harbored SMC1A gene c. 607A>G missense variant, and child 3 has harboredHDAC8 gene c. 628+ 1G>A splicing variant. All of the variants werede novo in origin. Conclusion All of the children were diagnosed with CdLS due to pathogenic variants of the associated genes, among which the variants of NIPBL and HDAC8 genes were unreported previously. Above finding has enriched the spectrum of pathogenic variants underlying CdLS.

    CorneliadeLange综合征NIPBL基因SMC1A基因HDAC8基因

      原文链接:
    • 万方数据

    G显带核型分析与荧光原位杂交在性染色体嵌合儿童中符合率的比较

    肖伟伟黄娟刘伟黎兵...
    12-16页
    查看更多>>摘要：目的 探讨G显带核型分析与荧光原位杂交(FISH)技术在性染色体嵌合儿童检测结果中的符合率。 方法 选取2020年4月至2021年5月于深圳市儿童医院就诊、进行间期性染色体FISH且可追溯到G显带核型结果的可疑性染色体异常患儿157例为研究对象，比较两种方法在性染色体嵌合儿童中的诊断符合率。 结果 G显带核型分析与FISH的异常检出率分别为26.1%(41/157)与22.9%(36/157)(P>0.05)。G显带核型分析结果中，性染色体纯合组141例(89.8%)，其中仅5例(3.5%)与FISH不符；性染色体嵌合组16例(10.2%)，其中11例(68.8%)与FISH不符。两组间两种检测方法结果符合率差异存在统计学差意义(P<0.05)。 结论 G显带核型分析和FISH的染色体异常检出率差异无统计学意义，但二者在性染色体嵌合组中符合率远低于纯合组，差异具有统计学意义，临床应考虑结合这两种方法对患者进行综合诊断。 Objective To explore the coincidence rate of G-banding karyotype analysis and fluorescence in situ hybridization (FISH) for the diagnosis of children with sex chromosome mosaicisms. Methods A retrospective analysis was carried out for 157 children with suspected sex chromosome abnormalities who had presented at Shenzhen Children′s Hospital from April 2021 to May 2022. Interphase sex chromosome FISH and G-banding karyotyping results were collected. The coincidence rate of the two methods in children with sex chromosome mosaicisms was compared. Results The detection rates of G-banding karyotype analysis and FISH were 26.1% (41/157) and 22.9% (36/157) , respectively (P>0.05). The results of G-banding karyotype analysis showed that 141 cases (89.8%) were in the sex chromosome homogeneity group, of which only 5 cases (3.5%) were inconsistent with the results of FISH. There were 16 cases (10.2%) in the sex chromosome mosaicism group, of which 11 cases (68.8%) were inconsistent with the results of FISH. There was a statistical difference between the two groups in the coincidence rate of the results of the two methods (P<0.05). Conclusion No significant difference was found between G-banding karyotype analysis and FISH in the detection rate of chromosome abnormalities. The coincidence rate in the mosaicism group was lower than that in the homogeneity group, and the difference was statistically significant. The two methods should be combined for clinical diagnosis.

    染色体G显带核型荧光原位杂交性染色体嵌合

      原文链接:
    • 万方数据

    四条染色体复杂易位合并9号染色体倒位1例

    孙倩夏玉林魏星李岭...
    16页
    查看更多>>摘要：患者 女，33岁，结婚3年妊娠2次均自然流产。本次因孕8周自然流产就诊，夫妻双方表型正常，否认不良用药或放射线接触史。在征得其知情同意后进行染色体检查，其丈夫核型未见异常，患者核型为46，XX，t(2；10)(q31；q11.2)，t(7；13)(q32；q12)，inv(9)(p12q13)，见图1。流产物高通量测序结果为seq[GRCh37]2p25.3-2q37.3×3，dup(7)(q32.3q36.3)，dup(13)(q11q12.11)。
      原文链接:
    • 万方数据

    CNV-seq在高危孕妇产前诊断中的应用价值

    向萍霞刘翎胡晞江周燕...
    17-20页
    查看更多>>摘要：目的 探讨低深度全基因组拷贝数变异测序(CNV-seq)在高危孕妇产前诊断中的应用价值。 方法 选取2018年7月至2019年11月于本院就诊的271例高危孕妇为研究对象。根据无创产前检测(NIPT)的结果，将271例高危孕妇分为NIPT阳性组(n＝83)和其他异常组(高龄、唐筛高风险、NIPT两次检测失败、不良孕产史、超声提示异常、自身表型异常)(n＝188)，应用CNV-seq技术对两组孕妇进行羊水细胞DNA的拷贝数变异(CNVs)检测，同时进行羊水细胞染色体核型分析，将二者的结果进行比对。 结果 在271例孕妇中，CNV-seq共检出致病性CNVs 56例(20.66%)，核型分析共发现染色体畸变52例(19.19%)，二者差异有统计学意义(P<0.05)。CNV-seq检测发现两组的CNVs的分型和分布差异具有统计学意义(P<0.05)。与NIPT阳性组相比，其他异常组的可能致病和意义未明CNVs的占比[2.41%(2/83)vs. 5.32%(10/188)]显著偏高(P<0.05)。 结论 可将CNV-seq作为高危孕妇的一线产前诊断方法，并作为羊水细胞染色体核型分析的补充诊断工具。因其他异常因素就诊的NIPT阴性高危孕妇中，可能致病及意义未明的CNVs的检出率偏高。 Objective To assess the application value of copy number variation sequencing (CNV-seq) for women with a high risk for fetal anomalies. Methods Based on the results of non-invasive prenatal testing (NIPT), 271 high-risk pregnant women were divided into NIPT positive group (n=83) and other anomaly group (advanced age, high risk by serological screening, repeated NIPT failure, adverse pregnancy history, abnormal ultrasound finding, and abnormal phenotype) (n=188). CNV-seq was carried out to detect copy number variations (CNVs) in amniocytic DNA from the two groups of pregnant women, and karyotyping analysis of the amniotic cells was carried out for verification and comparison. Results The amniocytes from 271 pregnant women were detected. The detection rate was 20.66% (56/271) for pathogenic CNVs by CNV-seq and 19.19% (52/271) for pathogenic karyotypes by karyotyping analysis. The difference was statistically significant (P<0.05). CNV-seq had shown that, compared with NIPT positive group, the detection rates for likely pathogenic CNVs and variants of unknown significance (VUS) in other abnormality group were significantly higher [2.41%(2/83)vs. 5.32%(10/188)](P<0.05). Conclusion CNV-seq can well suit the first-tier diagnosis for pregnant women suspected for fetal abnormality. In prenatal diagnosis settings, CNV-seq can identify additional and clinically significant cytogenetic abnormalities. In those with other abnormalities, the detection rates for likely pathogenic CNVs and VUS are higher than with the NIPT positive cases.

    低深度全基因组拷贝数变异测序产前诊断羊水核型分析

      原文链接:
    • 万方数据

    Joubert综合征二个家系的临床特征与遗传学分析

    赵登职楚艳杨科霍晓东...
    21-25页
    查看更多>>摘要：目的 探讨2个Joubert综合征家系的临床特征与遗传学病因。 方法 选取2020年11月27日、2021年1月22日于河南省人民医院就诊的2个Joubert综合征家系为研究对象。分析2个家系的临床特征，采集先证者及其家系成员外周血样，提取基因组DNA，进行高通量基因测序分析，应用Sanger测序对致病变异位点进行验证，并对家系2高危胎儿进行产前诊断。 结果 家系1先证者为胎儿，宫内孕23+5周，超声及磁共振均表现为"小脑蚓部发育不良"及"臼齿征"，引产胎儿无明显临床表型异常，基因检测提示其INPP5E基因存在c.812+3G>T和c.1828G>C复合杂合变异，临床诊断为Joubert综合征1型。家系2先证者表现为生长发育迟缓、智力低下、有特殊面容、肌张力低下、右足六趾畸形，磁共振提示小脑发育不良及"臼齿征"，先证者ARMC9基因存在c.485C>G和c.1878+1G>A复合杂合变异，临床诊断为Joubert综合征30型。产前诊断提示家系2胎儿ARMC9基因携带c.485C>G杂合变异，新生儿随访临床表型正常。 结论 INPP5E基因c.812+3G>T及c.1828G>C复合杂合变异和ARMC9基因c.485C>G及c.1878+1G>A复合杂合变异分别是家系1和家系2的遗传学致病原因，上述发现扩展了Joubert综合征的致病变异谱，为遗传咨询和产前诊断提供了依据。 Objective To explore the clinical characteristics and genetic basis of two Chinese pedigrees affected with Joubert syndrome. Methods Clinical data of the two pedigrees was collected. Genomic DNA was extracted from peripheral blood samples and subjected to high-throughput sequencing. Candidate variants were verified by Sanger sequencing. Prenatal diagnosis was carried out for a high-risk fetus from pedigree 2. Results The proband of pedigree 1 was a fetus at 23+ 5 weeks gestation, for which both ultrasound and MRI showed "cerebellar vermis malformation" and "molar tooth sign" . No apparent abnormality was noted in the fetus after elected abortion. The fetus was found to harbor c. 812+ 3G>T and c. 1828G>C compound heterozygous variants of the INPP5E gene, which have been associated with Joubert syndrome type 1. The proband from pedigree 2 had growth retardation, mental deficiency, peculiar facial features, low muscle tone and postaxial polydactyly of right foot. MRI also revealed "cerebellar dysplasia" and "molar tooth sign" . The proband was found to harbor c. 485C>G and c. 1878+ 1G>A compound heterozygous variants of the ARMC9 gene, which have been associated with Joubert syndrome type 30. Prenatal diagnosis found that the fetus only carried the c. 485C>G variant. A healthy infant was born, and no anomalies was found during the follow-up. Conclusion The compound heterozygous variants of the INPP5E and ARMC9 genes probably underlay the disease in the two pedigrees. Above finding has expanded the spectrum of pathogenic variants underlying Joubert syndrome and provided a basis for genetic counseling and prenatal diagnosis.

    Joubert综合征INPP5E基因ARMC9基因高通量测序产前诊断

      原文链接:
    • 万方数据

    46，XY，t(7；19)(q11.2；p13.1)平衡易位1例

    鞠彩宁蓝信强许芯李岭...
    25页
    查看更多>>摘要：患者 男，29岁，结婚3年，其妻自然流产1次，之后未避孕，未孕。患者平素性生活规律，1 ~ 2次/周，射精正常。查体：身高172 cm，第二性征发育正常，有喉结，身体健康，智力正常。双侧睾丸体积均约14 mL[参考范围为(19.8 ± 7.1)mL]，睾丸、附睾无压痛，未扪及结节，双侧精索静脉未触及曲张，精液检查未见异常。否认有毒、有害物质及放射线接触史，无不良嗜好。夫妇系非近亲结婚。本研究通过了医院伦理委员会的审查(WHFY-YXLLWYH-L2022010)，夫妻双方均签署了知情同意书。
      原文链接:
    • 万方数据

    AZFc微缺失在无精子症/严重少精子症男性中的发生率及遗传生殖学特点

    周赤燕王慧朱琴王路明...
    26-30页
    查看更多>>摘要：目的 探讨无精子因子c区(AZFc)微缺失在无精子症/严重少精子症男性中的发生率，并分析其与染色体核型、生殖激素的相关性及其对卵胞浆内单精子显微注射(ICSI)术后妊娠结局的影响。 方法 选取2013年1月1日至2020年12月31日于嘉兴学院附属妇儿医院就诊的1 364例无精子症/严重少精子症男性为研究对象。对无精子症/严重少精子症男性进行AZFc微缺失检测和染色体核型分析，比较AZFc缺失男性与对照组A(精液分析正常)、对照组B(无AZFc微缺失的无精子症/严重少精子症男性)的生殖激素水平。跟踪随访AZFc-ICSI夫妇的妊娠结局，将其受精率、优胚率和临床妊娠率与ICSI对照组进行比较。 结果 共检出AZFc微缺失51例，检出率为3.74%，其中7例存在染色体核型异常。与对照组A相比，AZFc微缺失男性的泌乳素(PRL)、卵泡刺激素(FSH)和促黄体素(LH)均有不同程度的升高(P<0.05)。与对照组B相比，仅PRL与FSH显著上调(P<0.05)。共有22对AZFc夫妇在本院接受ICSI辅助妊娠，其优胚率和临床妊娠率与ICSI对照组的差异无统计学意义(P>0.05)。 结论 AZFc微缺失在无精子症/严重少精子症男性中的发生率为3.74%，与染色体核型异常相关，并伴有不同程度的PRL、FSH和LH上调，但不会降低ICSI术后的临床妊娠率。 Objective To explore the incidence of azoospermia factor c (AZFc) microdeletion among patients with azoospermia or severe oligospermia, its association with sex hormone/chromosomal karyotype, and its effect on the outcome of pregnancy following intracytoplasmic sperm injection (ICSI) treatment. Methods A total of 1 364 males with azoospermia or severe oligospermia who presented at the Affiliated Maternity and Child Health Care Hospital of Jiaxing College between 2013 and 2020 were subjected to AZF microdeletion and chromosome karyotyping analysis. The level of reproductive hormones in patients with AZFc deletions was compared with those of control groups A (with normal sperm indices) and B (azoospermia or severe oligospermia without AZFc microdeletion). The outcome of pregnancies for the AZFc-ICSI couples was compared with that of the control groups in regard to fertilization rate, superior embryo rate and clinical pregnancy rate. Results A total of 51 patients were found to harbor AZFc microdeletion, which yielded a detection rate of 3.74%. Seven patients also had chromosomal aberrations. Compared with control group A, patients with AZFc deletion had higher levels of PRL, FSH and LH (P<0.05), whilst compared with control group B, only the PRL and FSH were increased (P<0.05). Twenty twoAZFc couples underwent ICSI treatment, and no significant difference was found in the rate of superior embryos and clinical pregnancy between the AZFc-ICSI couples and the control group (P>0.05). Conclusion The incidence of AZFc microdeletion was 3.74% among patients with azoospermia or severe oligospermia. AZFc microdeletion was associated with chromosomal aberrations and increased levels of PRL, FSH and LH, but did not affect the clinical pregnancy rate after ICSI treatment.

    生精障碍核型分析生殖激素辅助生殖

      原文链接:
    • 万方数据

    假性甲状旁腺功能减退症一个家系 GNAS基因的变异分析

    李茜黄佳代兴何嘉欢...
    31-35页
    查看更多>>摘要：目的 探讨1个假性甲状旁腺功能减退症家系的遗传学病因。 方法 选取2020年12月26日于河南省人民医院就诊的1个假性甲状旁腺功能减退症家系为研究对象。采用家系全外显子组测序(trio-WES)对先证者及其父母进行分析，筛选候选变异。随机选取50名健康个体进行限制性片段长度多态性检测，以排除基因位点多态性。采用短串联重复序列(STR)连锁分析确定致病变异的亲代来源。 结果 Trio-WES及Sanger测序结果显示先证者及母亲均携带GNAS基因c.121C>G(p.His41Asp)变异，家系其余成员及健康对照人群均未发现相同变异，检索数据库未见收录。依据美国医学遗传学与基因组学学会相关指南判断为可能致病变异。 结论 GNAS基因c.121C>G(p.His41Asp)变异可能是该家系的遗传学病因。上述发现丰富了GNAS基因的变异谱。 Objective To explore the genetic etiology of a Chinese pedigree affected with pseudohypoparathyroidism. Methods Peripheral blood samples of the proband and his parents were collected and subjected to trio-whole exome sequencing (trio-WES). Candidate variants were verified among the pedigree and 50 randomly selected healthy individuals through analysis of restriction fragment length polymorphism. Short tandem repeat (STR) linkage analysis was used to verify the parental origin of the pathogenic variants. Results Trio-WES and Sanger sequencing showed that the proband and his mother had both harbored a c. 121C>G (p.His41Asp) variant of theGNAS gene, which was not found in other family members and the 50 healthy controls. The variant was not found in international databases. Based on guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be likely pathogenic. Conclusion The novel c. 121C>G variant of theGNAS gene probably underlay the disease in this pedigree. Above finding has enriched the spectrum of GNAS gene variants.

    假性甲状旁腺功能减退症GNAS基因全外显子组测序短串联重复序列连锁分析

      原文链接:
    • 万方数据