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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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    天冬氨酰基葡萄糖胺尿症患儿1例的基因变异分析

    高爱民邓婉玲杨莹刘毓...
    87-91页
    查看更多>>摘要：目的 分析1例天冬氨酰基葡萄糖胺尿症(AGU)患儿的临床表型及遗传学病因。 方法 选取2021年1月25日于贵阳市妇幼保健院儿童内分泌科就诊的1例AGU患儿为研究对象。收集患儿的临床资料，对患儿进行全外显子组测序(WES)和基因组拷贝数变异测序(CNV-seq)，用Sanger测序对候选变异进行家系验证。 结果 患儿携带AGA基因c.319C>T(p.Arg107*)纯合无义变异，其父母均为同一变异的杂合子。患儿CNV-seq分析未见异常。上述变异在人群数据库及HGMD数据库中均未见收录，根据美国医学遗传学与基因组学学会相关指南判断为致病性(PVS1+PM2+PP3)。 结论 AGA基因c.319C>T纯合变异可能是本例AGU患儿的遗传学病因，上述发现为患儿父母的再次生育和产前诊断提供了依据。 Objective To explore the genetic basis for a child with Aspartylglucosaminuria (AGU). Methods Clinical data of the patient was analyzed. The child was subjected to trio-whole exome sequencing (WES) and copy number variation sequencing (CNV-seq), and candidate variant was verified by Sanger sequencing. Results The child was found to harbor homozygous c. 319C>T (p.Arg107*) nonsense variant of theAGA gene, for which both of his parents were heterozygous carriers. No abnormality was found by CNV-seq analysis. The c. 319C>T (p.Arg107*) variant was not found in population database, HGMD and other databases. Based on guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be pathogenic (PVS1+ PM2+ PP3). Conclusion The c. 319C>T variant of theAGA gene probably underlay the autosomal recessive AGU in this child. Above finding has enabled genetic counseling and prenatal diagnosis for his parents.

    天冬氨酰基葡萄糖胺尿症AGA基因致病变异全外显子组测序

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    常染色体显性Pallister-Hall综合征患儿1例的 GLI3基因变异分析

    侯欣微王健俊路羿余岱岳...
    92-95页
    查看更多>>摘要：目的 探讨1例Pallister-Hall综合征(PHS)患儿的临床特点及遗传学病因。 方法 选取2020年6月2日于南方医科大学珠江医院就诊的1例PHS患儿为研究对象。对患儿进行全外显子组检测，对候选变异进行Sanger测序家系验证。 结果 基因检测提示患儿携带GLI3基因(NM_000168)c.3320_3330delGGTACGAGCAG(p.G1107Afs×18)杂合变异，其父母均未携带相同变异。 结论 GLI3基因c.3320_3330delGGTACGAGCAG(p.G1107Afs×18)移码变异可能是患儿的遗传学病因。对于以下丘脑错构瘤、中心性多指(趾)畸形为主要特征的患儿，应考虑PHS并进行GLI3基因的变异检测。 Objective To explore the clinical and genetic characteristics of a child with Pallister-Hall syndrome (PHS). Methods DNA was extracted from peripheral blood sample from the child and subjected to whole exome sequencing. Suspected variants were verified by Sanger sequencing of his family members. Results Genetic testing revealed that the child has harbored a heterozygous c. 3320_3330delGGTACGAG CAG (p.G1107Afs×18) variant of the GLI3 gene. Neither parent was found to carry the same variant. Conclusion The c. 3320_3330delGGTACGAGCAG (p.G1107Afs×18) frameshift variant of the GLI3 gene probably underlay the pathogenesis of PHS in this child. Genetic testing should be considered for patients featuring hypothalamic hamartoma and central polydactyly.

    Pallister-Hall综合征全外显子组测序GLI3基因基因变异

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    罕见的8p部分缺失伴重复患儿1例的临床及遗传学分析

    陈新英潘汉斌曾书红江矞颖...
    96-100页
    查看更多>>摘要：目的 明确1例智力低下、语言发育迟缓及自闭症患儿的遗传学病因。 方法 选取2019年6月30日于泉州市妇幼保健院就诊的1例罕见8p部分缺失伴重复患儿为研究对象。采集患儿及其父母的外周血样，进行G显带染色体核型分析以及单核苷酸多态性微阵列(SNP-array)检测。 结果 患儿核型为46，XX，dup(8p？)，其父母均未见明显异常。SNP-array检测显示患儿染色体8p23.3p23.1区存在6.8 Mb的片段缺失，8p23.1p12区存在21.8 Mb的片段重复，上述拷贝数变异均为新发，并判断为致病变异。 结论 患儿的临床表型与染色体8p部分缺失重复相关，SNP-array检测对智力低下的患儿的诊断具有一定的价值。 Objective To explore the genetic etiology for a child featuring mental retardation, language delay and autism. Methods G-banding chromosomal karyotyping and single nucleotide polymorphism array (SNP-array) were carried out for the child and her parents. Results The child was found to have a 46, XX, dup(8p? ) karyotype, for which both of her parents were normal. SNP-array revealed that the child has harbored a 6.8 Mb deletion in 8p23.3p23.1 and a 21.8 Mb duplication in 8p23.1p12, both of which were verified as de novo pathogenic copy number variants. Conclusion The clinical features of the child may be attributed to the 8p deletion and duplication. SNP-array can facilitate genetic diagnosis for children featuring mental retardation in conjunct with other developmental anomalies.

    8p微缺失/微重复单核苷酸多态性微阵列智力障碍

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    5p缺失综合征胎儿1例的产前诊断

    王珺章卫国杨欢利马学娟...
    101-104页
    查看更多>>摘要：目的 对1例超声影像提示左足足内翻的胎儿进行遗传学分析，探讨其染色体拷贝数变异与临床表型的相关性。 方法 选取2020年10月14日于台州医院就诊的1例5p缺失综合征胎儿为研究对象。采集胎儿的羊水及其父母的外周血样，进行G显带核型分析，应用拷贝数变异测序(CNV-seq)检测胎儿染色体的微缺失与微重复，进一步用荧光原位杂交(FISH)技术进行家系验证。 结果 胎儿及其父母的G显带核型分析均未见明显异常，CNV-seq发现胎儿5号染色体存在23.12 Mb的拷贝数缺失，7号染色体存在21.46 Mb的拷贝数重复，FISH进一步验证胎儿母亲为隐匿性t(5；7)(p14.3；q33)携带者，胎儿的拷贝数变异遗传自母亲。 结论 CNV-seq联合FISH技术能有效诊断出隐匿性5p缺失综合征，避免患儿的出生，为产前遗传咨询提供理论依据。 Objective To explore the genetic basis for a fetus with club foot detected upon mid-pregnancy ultrasonography. Methods Amniotic fluid of the fetus and peripheral blood samples of its parents were collected and subjected to G-banding karyotype analysis and copy number variation sequencing (CNV-seq). The result was verified by fluorescence in situ hybridization (FISH). Results The fetus and its parents all had a normal karyotype. CNV-seq analysis revealed that the fetus has harbored a 23.12 Mb on chromosome 5 and a 21.46 Mb duplication on chromosome 7. FISH assay has verified that its mother has carried a cryptic t(5 7)(p14.3 q33) translocation. Conclusion CNV-seq combined with FISH can effectively detect cryptic chromosome aberrations, and can help to reduce severe birth defects and provide a basis for prenatal genetic counseling.

    5p缺失综合征拷贝数变异荧光原位杂交隐匿性易位

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    嵌合型4号环状染色体患儿1例的遗传学分析

    马灿玲王盈盈甄娜邵长喜...
    105-109页
    查看更多>>摘要：目的 探讨1例嵌合型4号环状染色体患儿核型的成因、临床表型及发病机制。 方法 选取2020年2月15日于滕州市妇幼保健院就诊的1例嵌合型4号环状染色体患儿为研究对象。收集患儿的临床资料，对其进行外周血染色体G显带核型分析、染色体微阵列分析(CMA)、荧光原位杂交(FISH)检测，并对文献进行回顾。 结果 患儿为足月小样低体重儿，具有特殊面容、动脉导管未闭、室间隔缺损。外周血染色体核型为mos 46，XY，r(4)(p16.3q35.2)[259]/45，XY，-4[25]/47，XY，r(4)(p16.3q35.2)，+r(4)(p16.3q35.2)[8]/46，XY，der(4)del(4)(p16.3)inv(4)(p16.3q31.1)[6]/46，XY，dic？r(4；4)(p16.3q35.2；p16.3q35.2)[4]/48，XY，r(4)(p16.3q35.2)，+r(4)(p16.3q35.2)×2[3]/46，XY，r(4)(p1？q2？)[2]；CMA检测结果为arr[GRCh37]4p16.3(68 345-2 981 614)×1；FISH检测结果为45，XY，-4[12]/45，XY，-4×2，+mar1.ish r1(4)(WHS-，D4Z1+)[1]/46，XY，-4，+mar1.ishr1(4)(WHS-，D4Z1+)[73]/46，XY，-4，+mar2.ishr2(4)(WHS-，D4Z1++)[1]/47，XY，-4，+mar1×2.ishr1(4)(WHS-，D4Z1+)×2[4]/46，XY，del(4)(p16.3)．ish del(4)(p16.3)(WHS-，D4Z1+)[9]。 结论 患儿的4号环状染色体为新发变异，在胚胎发育过程中产生了多种细胞系，形成同源嵌合体。4号环状染色体综合征临床表型多变，与其本身的不稳定性、是否存在嵌合体核型、是否伴有缺失/重复及其范围等有关。 Objective To explore the genetic basis, clinical phenotype and pathogenesis for a child with mosaicism ring chromosome 4. Methods Clinical data of the child was collected. Peripheral blood chromosomal karyotype G banding analysis, chromosomal microarray analysis (CMA), fluorescence in situ hybridization (FISH) were carried out for the child, in addition with a review of the literature. Results The child was born full-term with low birth weight, facial dysmorphism, patent ductus arteriosus and ventricular septal defect. His karyotype was determined as mos46, XY, r(4)(p16.3q35.2)[259]/45, XY, -4[25]/47, XY, r(4)(p16.3q35.2), + r(4)(p16.3q35.2)[8]/46, XY, der(4)del(4)(p16.3)inv(4)(p16.3q31.1)[6]/46, XY, dic? r(4 4)(p16.3q35.2 p16.3q35.2)[4]/48, XY, r(4)(p16.3q35.2), + r(4)(p16.3q35.2)×2[3]/46, XY, r(4)(p1? q2? )[2] CMA results was arr [GRCH37]4p16.3(68 345-2 981 614)×1 FISH results was 45, XY, -4[12]/45, XY, -4×2, + mar1.ish r1(4)(WHS-, D4Z1+ )[1]/ 46, XY, -4, + mar1.ishr1(4) (WHS-, D4Z1+ )[73]/46, XY, -4, + mar2.ishr2(4)(WHS-, D4Z1+ + )[1]/47, XY, -4, + mar1×2.ishr1(4) (WHS-, D4Z1+ )×2[4]/46, XY, del(4)(p16.3). ish del(4)(p16.3)(WHS-, D4Z1+ )[9]. Conclusion In this case, the ring chromosome 4 as a de novo variant has produced a number of cell lines during embryonic development and giren rise to mosaicism. The clinical phenotype of ring chromosome 4 is variable. The instability of the ring chromosome itself, presence of mosaicism, chromosome breakpoint and range of deletion and/or duplication may all affect the ultimate phenotype.

    4号环状染色体嵌合体足月小样低体重儿染色体核型分析染色体微阵列分析荧光原位杂交

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    ABO基因c.398T>C新变异导致Bweak表型的分子特性研究

    应燕玲洪小珍张晶晶马开荣...
    110-113页
    查看更多>>摘要：目的 探讨1例Bweak亚型个体的分子机制。 方法 选取2016年12月5日于浙江省血液中心献血的1例受试者为研究对象。利用血清学方法鉴定受试者的ABO表型，用体外酶活性试验测定其血清中B糖基转移酶(GTB)的活性。用PCR扩增ABO基因第5 ~ 7外显子及侧翼序列并确定其基因型，采用T-A克隆技术分离单倍体并进行测序验证。用ProtParam和PSIPRED软件分析蛋白的一级理化性质和二级结构。用PolyPhen-2、SIFT、PROVEAN三种软件分析错义变异对蛋白的作用效应。 结果 受试者血清学检测为Bweak亚型，血清中存在抗B抗体。体外酶活性试验显示其GTB活性显著降低。单倍体克隆测序分析发现B等位基因上存在c.398T>C错义变异，为一个新的B等位基因，可导致GTB第133位的苯丙氨酸替换为丝氨酸(p.Phe133Ser)。生物信息学分析提示上述替换对蛋白的一级和二级结构影响不明显，但变异蛋白的热力学能量增加6.07 kcal/mol，严重降低了热稳定性，生物信息学预测该变异对蛋白功能有害。 结论 新等位基因ABO*B.01-398C是引起Bweak亚型抗原弱表达的机制，生物信息学分析有助于评估其结构和功能的变化。 Objective To explore the molecular mechanism for an individual with Bweak subtype. Methods Serological methods were used to identify the proband′s phenotype. In vitro enzyme activity test was used to determine the activity of B-glycosyltransferase (GTB) in her serum. The genotype was determined by PCR amplification and direct sequencing of exons 5 to 7 and flanking sequences of the ABO gene. T-A cloning technology was used to isolate the haploids. The primary physical and chemical properties and secondary structure of the protein were analyzed with the ProtParam and PSIPRED software. Three software, including PolyPhen-2, SIFT, and PROVEAN, was used to analyze the effect of missense variant on the protein. Results Serological results showed that the proband′s phenotype was Bweak subtype and anti-B antibodies presented in her serum. In vitro enzyme activity assay showed that the GTB activity of the subject was significantly reduced. Analysis of the haploid sequence revealed a c. 398T>C missense variant on the B allele, which resulted in a novel B allele. The 398T>C variant has caused a p. Phe133S substitution at position 133 of the GTB protein. Based on bioinformatic analysis, the amino acid substitution had no obvious effect on the primary and secondary structure of the protein, but the thermodynamic energy of the variant protein has increased to 6.07 kcal/mol, which can severely reduce the protein stability. Meanwhile, bioinformatic analysis also predicted that the missense variant was harmful to the protein function. Conclusion The weak expression of the Bweak subtype may be attributed to the novel allele of ABO*B.01-398C. Bioinformatic analysis is helpful for predicting the changes in protein structure and function.

    Bweak变异型B糖基转移酶氨基酸置换生物信息学

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    LncRNA-GAS5基因多态性与广西人群系统性红斑狼疮的相关性研究

    陆玉兰蓝艳黄华佗黄艳新...
    114-120页
    查看更多>>摘要：目的 探讨lncRNA-GAS5基因rs55829688和rs75315904多态性与广西人群系统性红斑狼疮(SLE)易感性的相关性。 方法 选取2017年5月至2019年5月于右江民族医学院附属医院和百色市人民医院就诊的302例SLE患者与396名健康受试者为研究对象。采集SLE组与对照组受试者的静脉血样，提取基因组DNA，用SNPscan技术和Sanger测序对lncRNA-GAS5基因rs55829688和rs75315904位点进行基因分型与分析。 结果 rs55829688和rs75315904位点的基因型频率在两组之间差异无统计学意义(P>0.05)，而rs55829688位点C等位基因的频率在两组之间差异有统计学意义(P<0.05)；rs55829688位点C等位基因以及CT+CC基因型在伴有肾炎的患者中的频率显著低于不伴肾炎的患者(P<0.05)；单倍型分析发现，rs55829688 C/rs75315904 A等位基因频率在SLE组中显著低于对照组(P<0.05)。 结论 在广西人群中，lncRNA-GAS5基因rs55829688位点携带C等位基因可能降低SLE及其并发肾炎的发病风险，并且rs55829688 C/rs75315904 A单倍型也可能降低SLE的发病风险。 Objective To assess the association of rs55829688 and rs75315904 polymorphisms of the lncRNA-GAS5 gene with susceptibility to systemic lupus erythematosus (SLE) in Guangxi population. Methods Peripheral venous blood samples were collected from the SLE group and control group. Following extraction of genomic DNA, SNPscan and Sanger sequencing were carried out to determine the genotypes for the rs55829688 and rs75315904 loci of the lncRNA-GAS5 gene. Results No difference was found between the two groups with regard to the genotype frequencies for rs55829688 and rs75315904 (P>0.05). However, the frequencies of C allele of rs55829688 between the two groups was significantly different (P<0.05). In the SLE group, the frequencies of C allele and CT+ CC genotype for rs55829688 among SLE patients with nephritis were significantly lower than those of SLE patients without nephritis (P<0.05). In addition, haplotype analysis showed that the frequency of rs55829688 C/rs75315904 A allele in the SLE group was lower than that of the control group (P<0.05). Conclusion In Guangxi population, the carrier status of rs55829688 C allele of the lncRNA-GAS5 gene may reduce the risk of SLE and its complicated nephritis, and the rs55829688 C/rs75315904 A haplotype may reduce the risk for SLE.

    LncRNA-GAS5基因多态性系统性红斑狼疮

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    Charlevoix-Saguenay常染色体隐性痉挛性共济失调的致病机制研究进展

    付容丁曼卢祖能梁程红...
    121-124页
    查看更多>>摘要：Charlevoix-Saguenay常染色体隐性痉挛性共济失调(ARSACS)是一种由 SACS基因变异所致的早发罕见的神经变性疾病。 SACS基因位于染色体13q11区，编码sacsin蛋白，后者在运动系统的神经、尤其是小脑浦肯野细胞中高度表达。本文总结了sacsin蛋白的结构和功能异常导致ARSACS的机制，为该病的研究提供参考。 Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare and early-onset neurodegenerative disease caused by variants of theSACS gene which maps to chromosome 13q11 and encodes sacsin protein. Sacsin is highly expressed in large motor neurons, in particular cerebellar Purkinje cells. This article has provided a review for the structure and function of sacsin protein and the mechanisms underlying abnormalities of sacsin in ARSACS disease.

    Charlevoix-Saguenay常染色体隐性痉挛性共济失调SACS基因Sacsin蛋白

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    ALAS2 c．1108G>T新变异致X连锁性铁粒幼细胞性贫血1例

    贾茜婷何广胜许芯李岭...
    125-126页
    查看更多>>摘要：患者 男，29岁，10余年前出现面色苍白伴乏力，未予重视，逐渐在活动后出现明显的胸闷气喘，血常规提示重度贫血，于当地医院间断接受输血治疗。既往史：慢性乙型肝炎，肝硬化失代偿期半年，口服"替诺福韦"治疗。家族史：其胞弟具有类似的症状及病史。查体：重度贫血貌，全身皮肤黏膜无明显出血点、淤斑，未见肝掌、蜘蛛痣。全身浅表淋巴结未触及肿大，胸骨无压痛，肝脾肋下未及，双下肢凹陷型水肿。
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    ZBTB7A基因杂合变异致MNDLFH胎儿1例

    闫露露田丽蕴张玉鑫刘颖文...
    127页
    查看更多>>摘要：孕妇 30岁，G 1P 0，孕20 +1周B超提示胎儿双顶径、头围、腹围、股骨长度落后约1周，心脏超声提示为法洛四联症(图1)。孕妇夫妇体健，否认近亲结婚及家族遗传病史。经遗传咨询，于20 +5周选择终止妊娠，引产儿外观无明显异常。在签署知情同意书并通过医院伦理委员会审查(EC2020-048)后，采集引产组织和父母外周血样进行全外显子组测序，发现胎儿 ZBTB7A基因存在一个新发的错义变异c.232G>A(p.Asp78Asn)，既往未见报道(图2)。生物信息学分析提示ZBTB7A蛋白第78位的天冬氨酸在多个物种中高度保守(图3)，c.232G>A变异改变了ZBTB7A蛋白的α折叠、β转角以及无规则卷曲等二级结构，可能影响其功能(图4)。
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