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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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    McCune-Albright综合征患者3例的致病变异鉴定

    韩明辰米欢管鑫任秀智...
    186-190页
    查看更多>>摘要：目的 对3例McCune-Albright综合征(MAS)患者进行候选基因GNAS的变异鉴定，以明确其遗传学病因。 方法 选取2019年4月于山东省立医院就诊和2020年8月、2021年5月于北京协和医院就诊的共3例患者为研究对象。采用酚-氯仿法提取患者及其家系成员的外周血样基因组DNA，通过全外显子组测序(WES)对候选致病变异进行筛查，通过Sanger测序对候选变异进行家系验证。 结果 测序显示家系1患者存在GNAS基因第8外显子的c.601C>T(p.Arg201Cys)杂合错义变异；家系2和家系3患者均存在GNAS基因第8外显子的c.602G>A(p.Arg201His)杂合错义变异。两种变异均为已知致病变异，患者均为相应致病变异的嵌合体，但比例有所不同。 结论 WES是鉴定MAS等体细胞遗传病的有效方法。本研究联合应用WES和Sanger测序鉴定了MAS患者致病变异及其嵌合程度，并证实其与患者的表型无明显相关性，为遗传咨询和产前诊断提供了依据。 Objective To explore the genetic basis for three Chinese patients with McCune-Albright syndrome (MAS). Methods Three children who visited Shandong Provincial Hospital in April 2019 and Peking Union Medical College Hospital in August 2020 and May 2021 were selected as the research subjects. Peripheral blood samples of the probands and their family members were taken for the extraction of genomic DNA. Potential variants were screened by whole exome sequencing (WES), and candidate variants were validated by Sanger sequencing of the patients and their family members. Results The proband from family 1 was found to harbor a heterozygous c. 601C>T (p.R201C) missense variant in exon 8 of theGNAS gene, whilst the probands from families 2 and 3 were both found to harbor a heterozygous c. 602G>A (p.R201H) missense variant in exon 8 of theGNAS gene. Both variants were known to be pathogenic, and all probands were found to be mosaics for the corresponding variants but with various degrees. Conclusion WES can effectively diagnose MAS and other somatic genetic disorders. In this study, the combined WES and Sanger sequencing have verified the degree of mosaicisms of pathogenic variants in the three MAS patients, albeit no apparent correlation was found between the degree of mosaicisms and the phenotype of patients. Above finding has provided a basis for genetic counseling and prenatal diagnosis for the affected families.

    McCune-Albright综合征全外显子组测序GNAS基因错义变异

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    环状染色体患儿12例的临床表型及遗传学分析

    余宏盛胡晞江向萍霞刘翎...
    191-194页
    查看更多>>摘要：目的 探讨环状染色体在儿童生长发育期的发生率，分析其临床表型和遗传学特征。 方法 选取2015年1月至2021年8月因生长发育异常就诊的儿童7 574例，采集其外周血样进行G显带染色体核型分析。 结果 在7 574例患儿中，共检出12例环状染色体，检出率为0.16%，具体包括1例r(6)、2例r(9)、2例r(13)、1例r(14)、2例r(15)、1例r(21)以及3例r(X)。12例患儿均存在不同程度的表型异常，包括生长发育迟缓、智力低下、肢体畸形、先天性心脏病等。在具有相同断裂位点的2例r(9)患儿和2例r(15)患儿中，各有1例仅表现为生长发育迟缓，其余2例则合并r(9)有特殊面容、复杂先天性心脏病等。携带r(X)的患儿具有Turner综合征的部分表现。 结论 环状染色体是导致儿童生长发育及智力异常的重要原因，其临床表型复杂多样，临床医师应仔细采集这类患儿的病史，并尽早完善染色体检查以明确诊断。 Objective To explore the prevalence and clinical manifestations of ring chromosomes among children featuring abnormal development. Methods From January 2015 to August 2021, 7 574 children referred for abnormal development were selected, and their peripheral blood samples were subjected to G-banded chromosomal karyotyping analysis. Results Twelve cases of ring chromosomes were detected, which have yielded a prevalence of 0.16% and included 1 r(6), 2 r(9), 1 r(13), 1 r(14), 2 r(15), 1 r(21) and 3 r(X) among 7 574 children. The children had various clinical manifestations including growth and mental retardation, limb malformation, and congenital heart disease. For two children with r(9) and two with r(15) with similar breakpoints, one child with r(9) and one with r(15) only had growth retardation, whilst another with r(9) and another with r(15) also had peculiar facies and complex congenital heart disease. The r(X) has featured some manifestations of Turner syndrome. Conclusion Ring chromosomes are among the common causes for severe growth and mental retardation in children with diverse clinical phenotypes. Clinicians should pay attention to those with developmental anomalies and use chromosomal analysis to elucidate their genetic etiology.

    环状染色体核型分析临床表型

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    FGFR1变异导致唇腭裂胎儿1例

    段思琪李琳琳刘睿智杨潇...
    194页
    查看更多>>摘要：先证者 (图1，Ⅱ 5)男，系G 5P 4引产胎儿。先证者母亲(Ⅰ 2)，G 5P 4A 1L 2，第1、2胎为女孩(Ⅱ 1、Ⅱ 2)，临床表型均未见异常，第3胎为男孩，因唇腭裂引产，第4胎流产。第3、4胎均未留取样本进一步检测。第5胎为先证者，单侧唇腭裂。先证者父母临床表型均未见异常，否认近亲婚配史，否认家族遗传病史。取先证者引产组织及其父母外周血样进行全外显子组测序，提示先证者及其父亲存在 FGFR1基因(NM_023110.2)c.2152C>T(p.Arg718Cys)杂合错义变异，根据美国医学遗传学与基因组学学会(American College of Medical Genetics and Genomics，ACMG)指南，该变异被判为疑似致病变异(PM1+PM2+PP2+PP3)。先证者及其父母未检出与唇腭裂相关的1 M以上的致病染色体拷贝数变异和5 Mb以上的杂合性缺失变异，先证者母亲未检出任何变异。
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    低深度全基因组测序拷贝数变异分析技术在性发育异常患儿诊断中的应用价值

    夏俊珂侯雅勤代鹏赵振华...
    195-201页
    查看更多>>摘要：目的 探讨低深度全基因组测序拷贝数变异分析(CNV-seq)技术在性发育异常(DSD)患儿诊断中的应用价值。 方法 纳入2019年10月至2020年10月至郑州大学第一附属医院就诊的5例身材矮小或外阴发育异常的DSD患儿。在外周血染色体核型分析、全外显子组测序(WES)、SRY基因检测的基础上，进行CNV-seq检测以明确病因。 结果 患儿1和2的社会性别为女性，染色体核型均为46，XY，WES结果为阴性，CNV-seq结果分别为46，XY，+Y(1.4)和46，XY，-Y(0.75)。其余3例患儿均携带可疑的Y染色体，综合分析发现其核型分别为45，X[60]/46，X，del(Y)(q11.221)[40]、45，X，16qh+[76]/46，X，del(Y)(q11.222)，16qh+[24]和45，X[75]/46，XY[25]。 结论 联合运用CNV-seq等分子遗传学技术明确了46，XY DSD患儿的Y染色体拷贝数变异及45，X/46，XY DSD患儿可疑Y染色体的性质，为其临床诊疗提供了重要的依据。 Objective To assess the value of copy number variation sequencing (CNV-seq) for the diagnosis of children with disorders of sex development (DSD). Methods Five children with DSD who presented at the First Affiliated Hospital of Zhengzhou University from October 2019 to October 2020 were enrolled. In addition to chromosomal karyotyping, whole exome sequencing (WES), SRY gene testing, and CNV-seq were also carried out. Results Child 1 and 2 had a social gender of female, whilst their karyotypes were both 46, XY. No pathogenic variant was identified by WES. The results of CNV-seq were 46, XY, + Y(1.4) and 46, XY, -Y(0.75), respectively. The remaining three children have all carried an abnormal chromosome Y. Based on the results of CNV-seq, their karyotypes were respectively verified as 45, X[60]/46, X, del(Y)(q11.221)[40], 45, X, 16qh+ [76]/46, X, del(Y)(q11.222), 16qh+ [24], and 45, X[75]/46, XY[25]. Conclusion CNV-seq may be used to verify the CNVs on the Y chromosome among those with DSD and identify the abnormal chromosome in those with 45, X/46, XY. Above results have provided a basis for the clinical diagnosis and treatment of such children.

    性发育异常拷贝数变异45,X/46,XY低深度全基因组测序拷贝数变异分析

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    BCRP、LUNX基因mRNA表达水平与非小细胞肺癌患者的病理类型及分期的相关性

    陈栋韩文杰王培马红兵...
    202-207页
    查看更多>>摘要：目的 探讨乳腺癌耐药蛋白(BCRP)和肺特异性X蛋白(LUNX)基因的mRNA水平与非小细胞肺癌(NSCLC)患者病理类型及分期的相关性及其对于预后的价值。 方法 选取2015年6月至2018年6月河南大学淮河医院收治的89例患者为NSCLC组，以同期收治的55例肺良性病变患者为对照，检测两组患者外周血中BCRP、LUNX的mRNA表达水平，并分析其与临床病理特征及预后的相关性。 结果 NSCLC组外周血中BCRP、LUNX mRNA的阳性表达率显著高于肺良性病变组(P<0.05)；NSCLC患者BCRP mRNA的表达与分化程度、TNM分期有关(P<0.05)，与性别、年龄、吸烟、病理类型、淋巴结转移无关(P>0.05)；其LUNX mRNA的表达与分化程度、TNM分期、淋巴结转移有关(P<0.05)，与性别、年龄、吸烟、病理类型无关(P>0.05)；BCRP mRNA表达组与LUNX mRNA表达组的总体生存率均显著低于无表达组(P<0.05)；分化程度、TNM分期、淋巴结转移、BCRP mRNA表达、LUNX mRNA表达均为影响NSCLC患者预后的因素。 结论 NSCLC患者外周血中BCRP、LUNX mRNA的水平显著偏高，且BCRP mRNA的表达与分化程度、TNM分期有关，LUNX mRNA的表达与分化程度、TNM分期、淋巴结转移有关，二者可作为评估NSCLC患者预后的独立因素。 Objective To analyze the correlation between the mRNA levels of breast cancer resistance protein (BCRP) and lung-specific X protein (LUNX) genes with pathological types and stages of patients with non-small cell lung cancer (NSCLC) and their significance for prognosis. Methods Eighty nine patients with NSCLC admitted to Huaihe Hospital of Henan University between June 2015 and June 2018 were recruited, with 55 patients with benign lung lesions admitted during the same period of time selected as the control group. The mRNA levels of BCRP and LUNX genes were detected in the peripheral blood samples from the two groups, and their correlation with the clinicopathological characteristics and prognosis of the patients was analyzed. Results The expression rates of BCRP and LUNX mRNA in the NSCLC group were significantly higher compared with the control group (P<0.05). The level ofBCRP mRNA of the NSCLC patients has correlated with the degree of differentiation and TNM staging (P<0.05), but not with gender, age, smoking, pathological types and lymph node metastasis (P>0.05). The level ofLUNX mRNA of them has correlated with the degree of differentiation, TNM staging and lymph node metastasis (P<0.05), but not with gender, age, smoking, and pathological types (P>0.05). Compared with those with no expression, the overall survival rate of patients withBCRP and LUNX expression was significantly lower (P<0.05). The degree of differentiation, TNM staging, lymph node metastasis, and expression of theBCRP and LUNX mRNA may all affect the prognosis of the patients. Conclusion The levels of BCRP and LUNX mRNA in the peripheral blood of patients with NSCLC are significantly increased. The expression of BCRP mRNA is correlated with the degree of differentiation and TNM staging, whilst the expression of LUNX mRNA is correlated with the differentiation degree, TNM staging and lymph node metastasis. Both may be used as independent predictors for the prognosis of patients with NSCLC.

    非小细胞肺癌乳腺癌耐药蛋白肺特异性X蛋白病理类型TNM分期预后

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    口-面-指综合征一个家系的表型与遗传学分析

    程青青楚伟霍平石子佳...
    208-212页
    查看更多>>摘要：目的 探讨1个口-面-指综合征Ⅰ型(OFD1)家系的临床表型及遗传学原因。 方法 选取2021年3月17日至河北省人民医院就诊的1个OFD1家系为研究对象。收集先证者临床资料对该家系的成员进行家系全外显子组测序(WES)，并通过Sanger测序进行验证。 结果 先证者表现为宽眼距、宽鼻根、鼻尖扁平，分叶舌、舌赘生物，左手小指呈弯曲状，右手小指与无名指并指，智力及语言发育落后。WES结果提示先证者及其女儿、妹妹和母亲均携带OFD1基因c.224A>G(p.Asn75Ser)杂合变异，家系中的其他成员未携带同样的变异。 结论 c.224A>G(p.Asn75Ser)杂合变异可能是导致该家系表型异常的原因，上述发现丰富了OFD1基因的变异谱。 Objective To explore the clinical phenotype and genetic basis for a Chinese pedigree affected with Oral-facial-digital syndrome type Ⅰ (OFD1). Methods A pedigree with OFD1 who presented at Hebei General Hospital on March 17, 2021 was selected as the subject. Clinical data of the child was collected. Trio-whole exome sequencing (trio-WES) was carried out for the proband and members of her pedigree, and candidate variant was verified by Sanger sequencing. Results The proband has featured hypotelorism, broad nasal root, flat nasal tip, lobulated tongue, tongue neoplasia, camptodactyly of left fifth finger, syndactyly of right fourth and fifth fingers, and delayed intellectual and language development. Trio-WES revealed that the proband and her daughter, sister and mother have harbored a heterozygous c. 224A>G (p.Asn75Ser) variant of theOFD1 gene.The same variant was not found among healthy members from her pedigree. Conclusion The c. 224A>G (p.Asn75Ser) variant probably underlay the OFD1 in this pedigree. Above discovery has enriched the spectrum ofOFD1 gene variants.

    口-面-指综合征OFD1基因纤毛病胼胝体发育不全

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    神经发育障碍伴或不伴自闭症特征和(或)脑结构异常患儿1例的 NOVA2基因变异分析

    张广宇李三松杨磊王明梅...
    213-216页
    查看更多>>摘要：目的 探讨1例神经发育障碍伴或不伴自闭症特征和(或)脑结构异常患儿的遗传学病因。 方法 选取2021年7月至郑州大学第三附属医院就诊的1例NEDASB患儿为研究对象。抽取患儿及其父母的外周血样，采用高通量测序技术对患儿进行基因检测，对候选变异进行Sanger测序验证以及生物信息学分析。 结果 基因检测结果显示患儿携带NOVA2基因c.820_828delinsCTTCA(p.Thr274Leufs*121)杂合变异。其父母均未携带相同的变异。根据美国医学遗传学与基因组学学会相关指南，判断其为致病变异。 结论 NOVA2基因c.820_828delinsCTTCA(p.Thr274Leufs*121)杂合变异可能是本例患儿的遗传学病因。上述发现丰富了NOVA2基因的变异谱，为遗传咨询及产前诊断提供了依据。 Objective To explore the genetic basis for a child with Neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities(NEDASB). Methods A child with NEDASB who presented the Third Affiliated Hospital of Zhengzhou University in July 2021 was selected as the subject. Peripheral blood samples of the child and her parents were collected and subjected to high-throughput sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. Results The child was found to harbor a heterozygous c. 820_828delinsCTTCA (p.Thr274Leufs*121) variant of the NOVA2 gene, for which both of her parents were of wild type. The variant was predicted as pathogenic based on the guidelines from the American College of Medical Genetics and Genomics. Conclusion The heterozygous c. 820_828delinsCTTCA (p.Thr274Leufs*121) variant of the NOVA2 gene probably underlay the disease in this child. Above finding has enriched the spectrum of NOVA2 gene variants and provided a basis for genetic counseling and prenatal diagnosis for this family.

    神经发育障碍NOVA2基因高通量测序

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    GLI2基因变异所致Culler-Jones综合征患儿1例的临床及遗传学分析

    范言诗丁曙霞吴军华邱海燕...
    217-221页
    查看更多>>摘要：目的 分析1例生长缓慢、多指畸形患儿的基因变异，明确其致病原因。 方法 选取2021年5月因"发现生长速度减慢2年余"至宁波市妇女儿童医院就诊的1例患儿为研究对象。采集患儿及其父母的外周血样，提取DNA，对患儿进行全外显子组测序，用Sanger测序对GLI2基因的候选变异进行家系验证。 结果 患儿GLI2基因存在c.3670C>T(p.Q1224*)杂合变异，导致编码蛋白的多肽链合成提前终止，其父母均未检测到相同的变异。 结论 患儿被确诊为Culler-Jones综合征。GLI2基因的c.3670C>T(p.Q1224*)杂合变异可能是其遗传学病因。 Objective To explore the genetic basis for a child featuring short stature and postaxial polydactyly. Methods A case of child who presented at Ningbo Women & Children′s Hospital in May 2021 due to the" discovery of growth retardation for more than two years" was selected as the subject. Peripheral blood samples of the child and his parents were collected for the extraction of genomic DNA. Whole exome sequencing was carried out for the child, and candidate variant was verified by Sanger sequencing of his family members. Results The child was found to harbor a heterozygous c. 3670C>T (p.Q1224) variant of theGLI2 gene, which may lead to premature termination of protein translation. The variant was not detected in either parent. Conclusion The child was diagnosed with Culler-Jones syndrome. The c. 3670C>T (p.Q1224*) variant of theGLI2 gene probably underlay the disease in this child.

    Culler-Jones综合征GLI2基因全外显子组测序

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    KMT2A基因变异所致Wiedemann-Steiner综合征患儿1例的临床特征及遗传学分析

    艾奇陈云陈森梁程红...
    222-225页
    查看更多>>摘要：目的 探讨1例Wiedemann-Steiner综合征(WSS)患儿的临床特征及遗传学病因。 方法 选取2015年7月就诊于天津市儿童医院血液科的1例WSS患儿为研究对象。收集患儿的临床资料，采集患儿及其父母的外周血样，提取基因组DNA，对患儿进行全外显子组测序，用Sanger测序对候选变异进行家系验证。 结果 患儿主要表现为全血细胞减少、智力及生长发育落后、特殊面容。全外显子组测序显示其携带KMT2A基因c.7804delA(p.M2602Cfs*39)杂合变异。Sanger测序显示其父母未携带相同的变异。该变异既往未见报道。根据美国医学遗传学和基因组学学会相关指南，判定其为致病性变异(PVS1+PS2+PM2)。 结论 KMT2A基因c.7804delA(p.M2602Cfs*39)杂合变异可能为该WSS征患儿的致病原因。上述发现拓宽了KMT2A基因的变异谱和临床表型谱。 Objective To explore the clinical features and genetic etiology of a child with Wiedemann-Steiner syndrome (WSS). Methods A child with WSS who was admitted to the Hematology Department of Tianjin Children′s Hospital in May 2021 was selected as the subject. Clinical data of the child was collected. Peripheral blood samples were collected from the child and his parents for the extraction of genomic DNA. The child was subjected to whole exome sequencing, and candidate variant was verified by Sanger sequencing of the child and his parents. Results The main clinical features of the child have included pancytopenia, growth and mental retardation, and facial dysmorphism. Whole exome sequencing revealed that the child has harbored a heterozygous variant of the KMT2A gene, namely c. 7804delA (p.M2602Cfs*39). Sanger sequencing verified the variant to be de novo in origin. The variant was unreported previously and predicted to be pathogenic based on the guidelines of American College of Medical Genetics and Genomics (PVS1+ PS2+ PM2). Conclusion The heterozygous c. 7804delA (p.M2602Cfs*39) variant of the KMT2A gene probably underlay the WSS in this child. Above finding has enriched the mutational spectrum and clinical phenotypes of the KMT2A gene.

    Wiedemann-Steiner综合征KMT2A基因全血细胞减少

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    HNRNPK基因新发变异导致新生儿Au-Kline综合征1例的临床特征与遗传学分析

    陈珺戴立英郑洪刘光辉...
    226-229页
    查看更多>>摘要：目的 探讨1例Au-Kline综合征(AKS)新生儿的临床表型与基因特征。 方法 回顾性分析2021年1月收治入安徽医科大学附属省儿童医院的1例AKS患儿的临床资料及基因变异信息，并以"Au-Kline syndrome""Au-Kline综合症""HNRNPK""AKS"为关键词进行检索，分别检索2000年1月1日至2020年12月31日的万方数据、中国知网、PubMed数据库的相关文献，总结分析该病临床特点及遗传学特征。 结果 本例患儿为男性，临床表现为喂养困难、肌张力低下、上颚缺如至悬雍垂处及特殊面容，家系全外显子组测序检测结果提示该例患儿HNRNPK基因发生移码变异c.478dupA(p.Ile160AsnfsTer7)。Sanger测序显示该例患儿的父母未见异常，可能为新发变异。查阅数据库未见该变异有收录，根据美国医学遗传学与基因组学学会变异评级指南评级为致病性(PVS1+PS2+PM2_Supporting)。通过文献检索，纳入研究AKS患儿14例，均为HNRNPK基因新发变异，临床表现均有生长发育迟缓、运动发育迟缓及不同程度智力障碍等，具有可辨识度的特殊面容，其余高频表型为先天性心脏畸形。 结论 HNRNPK基因c.478dupA移码变异导致提前终止编码氨基酸可能是该患儿发生AKS的遗传学病因。在鉴别诊断上对于先天性多发畸形伴智力障碍亦或歌舞伎综合征患儿时，临床医师应考虑AKS的可能性。 Objective To explore the clinical phenotype and genetic basis of a neonate with Au-Kline syndrome (AKS). Methods Clinical data and result of genetic testing of a neonate with AKS who was admitted to the Affiliated Provincial Children′s Hospital of Anhui Medical University in January 2021 were retrospectively analyzed. Relevant literature was searched from the Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure and PubMed databases using key words "Au Kline syndrome" , "Au-Kline syndrome" , " HNRNPK" and "AKS" . The research period was set as from January 1, 2000 to December 31, 2020. Results The male newborn has manifested feeding difficulties, hypotonia, absence of the upper jaw to the uvula and facial dysmorphism. Trio-whole exome sequencing revealed that he has harbored a frameshift c. 478dupA (p.Ile160AsnfsTer7) variant of the HNRNPK gene, which was varified by Sanger sequencing to have a de novo origin. The variant has not been included in the databases. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was rated as pathogenic (PVS1+ PS2+ PM2_Supporting). Literature retrieval has identified 14 children with AKS and de novo mutations of the HNRNPK gene. Their clinical manifestations have included growth and motor retardation, various degree of mental retardation, facial dysmorphism and a high frequency of congenital heart malformations. Conclusion The AKS in this child may be attributed to the the c478dupA frameshifting variant of the HNRNPK gene. Diagnosis of AKS should be suspected for children with mental retardation and multiple congenital malformation syndromes including Kabuki syndrome.

    Au-Kline综合征HNRNPK基因智力障碍全外显子组测序新生儿

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