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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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    涉及 ACAN基因的15q25.3q26.1缺失致家族性矮小一个家系的遗传学分析

    冯跃英丁曙霞张萍萍方洁...
    478-482页
    查看更多>>摘要：目的 探讨1个矮小家系的遗传学病因，为临床诊断及制定治疗策略提供参考。 方法 选取2020年7月在宁波市妇女儿童医院确诊为家族性矮小(FSS)的1例患儿及其父母、祖父母以及外祖父母为研究对象。收集先证者及其上述家系成员的临床资料，采集外周血样，提取基因组DNA，对先证者进行全外显子组测序(WES)，对先证者及其父母、祖父母进行染色体微阵列分析(CMA)，采用重组人生长激素(rhGH)对先证者进行治疗并评估效果。 结果 先证者身高为87.7 cm(-3 s)，其父亲身高为152 cm(-3.39 s)，母亲及祖父母身高无明显异常。WES提示先证者染色体15q25.3-q26.1区存在4.35 Mb缺失，CMA提示先证者及其父亲15号染色体长臂均存在4.342 Mb的杂合缺失[arr[hg19]15q25.3-q26.1(86828614_91170208)×1]，该缺失片段涉及与矮小表型密切相关的ACAN基因。母亲及祖父母CMA检测均未见异常。上述缺失在人群数据库及相关文献中均未见报道，根据美国医学遗传学与基因组学学会(ACMG)相关指南，评估为致病性拷贝数变异。用rhGH治疗14个月后，先证者身高增加至98.5 cm(-2.07 s)，疗效显著。 结论 涉及ACAN基因的染色体15q25.3-q26.1微缺失可能导致FSS，短期rhGH治疗可有效改善这类患儿的身高。 Objective To analyze the genetic etiology of a Chinese pedigree affected with short stature. Methods A child with familial short stature (FSS) who had presented at the Ningbo Women and Children′s Hospital in July 2020 and his parents and paternal and maternal grandparents were selected as the study subjects. Clinical data of the pedigree was collected, and the proband was subjected to routine growth and development assessment. Peripheral blood samples were collected. The proband was subjected to whole exome sequencing (WES), and the proband, his parents and grandparents were subjected to chromosomal microarray analysis (CMA). Results The height of the proband and his father was 87.7cm (-3 s) and 152 cm (-3.39 s) respectively. Both of them were found to harbor a 15q25.3-q26.1 microdeletion, which has encompassed the whole of the ACAN gene which is closely associated with short stature. The CMA results of his mother and grandparents were all negative, and above deletion has not been included in population database and related literature, and was rated as pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). After 14 months of rhGH treatment, the height of the proband has increased to 98.5 cm (-2.07 s). Conclusion The 15q25.3-q26.1 microdeletion probably underlay the FSS, in this pedigree. Short-term rhGH treatment can effectively improve the height of the affected individuals.

    染色体缺失ACAN基因家族性矮小生长激素

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    母源性染色体内插入致18q21.2-q22.3重复和缺失后代家系的遗传学分析

    周家红周攀吕志宇张晖...
    483-489页
    查看更多>>摘要：目的 为1例具有全面发育障碍患儿生育史的孕妇提供产前诊断、家系分析和遗传咨询。 方法 选取2021年8月在西南医科大学附属医院接受产前诊断的孕妇作为研究对象，采集先证者、孕妇及其丈夫的外周血样以及胎儿的羊水样本，对其进行G显带染色体核型分析以及基因组拷贝数变异测序(CNV-seq)，根据美国医学遗传学与基因组学学会(ACMG)相关指南判读变异的致病性，通过家系分析对变异进行溯源，并评估其再发风险。 结果 孕妇、胎儿、先证者的染色体核型依次为46，XX，ins(18)(p11.2q21q22)、46，X？，rec(18)dup(18)(q21q22)ins(18)(p11.2q21q22)mat和46，XY，rec(18)del(18)(q21q22)ins(18)(p11.2q21q22)mat，孕妇丈夫染色体核型未见异常。CNV-seq检测提示胎儿18q21.2-q22.3区存在19.73 Mb重复，先证者18q21.2-q22.3区存在19.77 Mb缺失。重复和缺失片段均与孕妇染色体的插入片段相同。根据ACMG指南，均评估为致病性变异。 结论 孕妇携带的18q21.2-q22.3染色体内插入导致了2个子代18q21.2-q22.3区的重复和缺失。上述结果为该家系的遗传咨询提供了依据。 Objective To provide prenatal diagnosis, pedigree analysis and genetic counseling for a pregnant woman who had given birth to a child featuring global developmental delay. Methods A pregnant woman who underwent prenatal diagnosis at the Affiliated Hospital of Southwest Medical University in August 2021 was selected as the study subject. Peripheral blood samples were collected from the woman, her husband and child, in addition with amniotic fluid sample during mid-pregnancy. Genetic variants were detected by G-banded karyotyping analysis and copy number variation sequencing (CNV-seq). Pathogenicity of the variant was predicted based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Candidate variant was traced in the pedigree to assess the recurrence risk. Results The karyotypes of the pregnant woman, her fetus, and affected child were 46, XX, ins(18)(p11.2q21q22), 46, X? , rec(18)dup(18)(q21q22)ins(18)(p11.2q21q22)mat and 46, XY, rec(18)del(18)(q21q22)ins(18)(p11.2q21q22)mat, respectively. Her husband was found to have a normal karyotype. CNV-seq has revealed a 19.73 Mb duplication at 18q21.2-q22.3 in the fetus and a 19.77 Mb deletion at 18q21.2-q22.3 in her child. The duplication and deletion fragments were identical to the insertional fragment in the pregnant woman. Based on the ACMG guidelines, the duplication and deletion fragments were both predicted to be pathogenic. Conclusion The intrachromosomal insertion of 18q21.2-q22.3 carried by the pregnant woman had probably given rise to the 18q21.2-q22.3 duplication and deletion in the two offspring. Above finding has provided a basis for genetic counseling for this pedigree.

    染色体内插入18q21.2-q22.318q部分三体18q部分单体孕妇

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    12三体嵌合伴严重心脏缺陷胎儿1例的遗传学分析及文献回顾

    尹婷王志伟谭娟汤欣欣...
    490-494页
    查看更多>>摘要：目的 对1例12三体嵌合伴严重心脏缺陷的胎儿进行遗传学研究，探讨其染色体异常与临床表型以及妊娠结局之间的关系。 方法 选取于2021年5月17日因"超声提示胎儿心脏发育异常"就诊于连云港市妇幼保健院的1例33岁孕妇及其胎儿作为研究对象。收集胎儿的临床资料，采集孕妇的羊水样本，对其进行染色体G显带核型分析及染色体微阵列分析(CMA)，追踪随访新生儿的情况。在中国知网、万方数据以及PubMed数据库中以"12三体嵌合""mosaic trisomy 12""trisomy 12 mosaicism"为关键词，检索1992年6月1日至2022年6月1日的相关文献并进行回顾分析。 结果 孕妇33岁，孕22+6周超声显示胎儿心脏发育异常，疑似肺静脉异位引流。G显带分析显示胎儿染色体核型为mos 47，XX，+12[1]/46，XX[73]，嵌合比例为1.35%。CMA检测结果提示胎儿12号染色体存在约18%的三体型嵌合。孕妇于孕39周分娩1女婴，存在严重的先天性心脏病，头围偏小，耳位低及外耳畸形，3个月后夭折。文献回顾共检索到9篇文献，12三体嵌合活产儿的临床表型因嵌合影响不同的器官而表现多样，可导致先天性心脏病或其他脏器及面部畸形，导致不良的妊娠结局。 结论 12三体嵌合是导致新生儿严重心脏缺陷的原因，超声检查结果对胎儿的预后评估具有重要的价值。 Objective To explore the genetic basis for a fetus with severe heart defect and mosaic trisomy 12, and the correlation between chromosomal abnormalities and clinical manifestations and pregnancy outcome. Methods A 33-year-old pregnant woman who presented at Lianyungang Maternal and Child Health Care Hospital on May 17, 2021 due to abnormal fetal heart development revealed by ultrasonography was selected as the study subject. Clinical data of the fetus were collected. Amniotic fluid sample of the pregnant women was collected and subjected to G-banded chromosomal karyotyping and chromosomal microarray analysis (CMA). The CNKI, WanFang and PubMed databases were searched with key words, with the retrieval period set as from June 1, 1992 to June 1, 2022. Results For the 33-year-old pregnant woman, ultrasonography at 22+ 6 gestational weeks had revealed abnormal fetal heart development and ectopic pulmonary vein drainage. G-banded karyotyping showed that the fetus has a karyotype of mos 47, XX, + 12[1]/46, XX[73], with the mosaicism rate being 1.35%. CMA results suggested that about 18% of fetal chromosome 12 was trisomic. A newborn was delivered at 39 weeks of gestation. Follow-up confirmed severe congenital heart disease, small head circumference, low-set ears and auricular deformity. The infant had died 3 months later. The database search has retrieved 9 reports. Literature review suggested that the liveborn infants with mosaic trisomy 12 had diverse clinical manifestations depending on the affected organs, which had included congenital heart disease and/or other organs and facial dysmorphisms, resulting in adverse pregnancy outcomes. Conclusion Trisomy 12 mosaicism is an important factor for severe heart defects. The results of ultrasound examination have important value for evaluating the prognosis of the affected fetuses.

    12三体嵌合低比例嵌合先天性心脏病孕妇胎儿

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    继发不孕女性1例的Fra(16)(q22)脆性位点的遗传学分析

    谢成秀高崇兰康涵刘青松...
    495-499页
    查看更多>>摘要：目的 探讨1例继发不孕女性Fra(16)(q22)(FRA16B)脆性位点的遗传学机制。 方法 选取2021年10月5日因"继发不孕"就诊于成都市妇女儿童中心医院的1例28岁的携带FRA16B女性患者作为研究对象，采集其外周血样进行染色体G显带核型分析、单核苷酸多态性微阵列检测(SNP-array)、QF-PCR以及荧光原位杂交(FISH)检测。 结果 患者共发现5种染色体核型，具体为mos 46，XX，Fra(16)(q22)[42]/46，XX，del(16)(q22)[4]/47，XX，del(16)，+chtb(16)(q22-qter)[4]/ 46，XX，tr(16)(q22)[2]/46，XX[71]，但其SNP-array、QF-PCR和FISH检测结果均未见明显异常。 结论 通过遗传学手段发现了1例FRA16B女性患者。上述发现有助于其后续怀孕时的遗传咨询。 Objective To explore the genetic basis for a Fra(16)(q22)(FRA16B) fragile site in a female with secondary infertility. Methods The 28-year-old patient was admitted to Chengdu Women′s and Children′s Central Hospital on October 5, 2021 due to secondary infertility. Peripheral blood sample was collected for G-banded karyotyping analysis, single nucleotide polymorphism array (SNP-array), quantitative fluorescent polymerase chain reaction (QF-PCR) and fluorescence in situ hybridization (FISH) assays. Results The patient was found to harbor 5 mosaic karyotypes involving chromosome 16 in a total of 126 cells, which yielded a karyotype of mos 46, XX, Fra(16)(q22)[42]/46, XX, del(16)(q22)[4]/47, XX, del(16), + chtb(16)(q22-qter)[4]/46, XX, tr(16)(q22)[2]/46, XX[71]. No obvious abnormality was found by SNP-array, QF-PCR and FISH analysis. Conclusion A female patient with FRA16B was identified by genetic testing. Above finding has enabled genetic counseling of this patient.

    脆性位点Fra(16)(q22)染色体核型分析

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    细胞色素P450的基因多态性与缺血性脑卒中的相关性研究

    齐林刘永芳祁萌彭莹娟...
    500-504页
    查看更多>>摘要：目的 探讨细胞色素P450(CYP450)的基因多态性与缺血性脑卒中(IS)发病的相关性。 方法 选取2020年1月至2022年8月于郑州市第七人民医院神经内科就诊的390例IS患者为研究对象，将其纳入病例组；选取同期于本院接受体检的410例健康人纳入对照组。收集受试者的临床资料，包括年龄、性别、身体质量指数(BMI)、吸烟史、实验室检查结果等，采用χ2检验与独立样本t检验对临床资料进行统计学比较，进一步采用多因素非条件Logistic回归分析法，分析影响IS发生的非遗传性独立风险因素。采集受试者的空腹外周血样，用Sanger测序检测CYP2C19基因rs4244285、rs4986893、rs12248560和CYP3A5基因rs776746位点的基因型，使用SNPStats在线软件计算各基因型的频率，分析基因型、显性、隐性和加性模型与IS的相关性。 结果 病例组受试者的总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)、载脂蛋白B(Apo-B)和同型半胱氨酸(Hcy)水平等指标均高于对照组，而高密度脂蛋白(HDL-C)和载脂蛋白A1(Apo-A1)水平等指标均低于对照组，差异均具有统计学意义(P<0.05)；多因素非条件Logistic回归分析显示，TC(95%CI ＝ 1.13-1.92，P＝0.02)、LDL-C(95%CI ＝ 1.03-2.25，P＝0.03)、Apo-A1(95%CI ＝ 1.05-2.08，P＝0.04)、Apo-B(95%CI ＝ 1.7-4.22，P<0.01)、Hcy(95%CI ＝ 1.12-1.83，P＝0.04)均为影响IS发生的非遗传性独立风险因素。CYP2C19与CYP3A5基因各位点的多态性与IS发病风险的分析结果显示，CYP2C19基因rs4244285位点的AA基因型、rs4986893位点的AG基因型和A等位基因、CYP3A5基因rs776746位点的GG基因型和G等位基因与IS显著相关，并且rs4244285、rs4986893和rs776746位点分别在隐性/加性模型、显性模型和显性/加性模型中也与IS显著相关。 结论 TC、LDL-C、Apo-A1、Apo-B及Hcy均可影响IS的发生，CYP2C19与CYP3A5基因多态性与IS密切相关，证实CYP450的基因多态性可增加IS的发病风险，可为临床诊断该病的患者提供更多的依据。 Objective To assess the association of cytochrome P450 (CYP450) gene polymorphisms with the occurrence of ischemic stroke (IS). Methods From January 2020 to August 2022, 390 IS patients treated at the Zhengzhou Seventh People′s Hospital were enrolled as the study group, and 410 healthy individuals undergoing physical examination during the same period were enrolled as the control group. Clinical data of all subjects were collected, which included age, sex, body mass index (BMI), smoking history and results of laboratory tests. Chi-square test and independent sample t test were used for comparing the clinical data. Multivariate logistic regression analysis was used to analyze the non-hereditary independent risk factors for IS. Fasting blood samples of the subjects were collected, and the genotypes of rs4244285, rs4986893, rs12248560 of the CYP2C19 gene and rs776746 of the CYP3A5 gene were determined by Sanger sequencing. The frequency of each genotype was calculated by using SNPStats online software. The association between the genotype and IS under the dominant, recessive and additive models was analyzed. Results The levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-C), apolipoprotein B (Apo-B) and homocysteine (Hcy) of the case group were significantly higher than those of the control group, whilst the levels of high density lipoprotein (HDL-C) and apolipoprotein A1 (Apo-A1) were significantly lower (P<0.05). Multivariate Logistic regression analysis showed that TC (95%CI = 1.13-1.92, P=0.02), LDL-C (95%CI = 1.03-2.25, P=0.03), Apo-A1 (95%CI = 1.05-2.08, P=0.04), Apo-B (95%CI = 1.7-4.22, P<0.01) and Hcy (95%CI = 1.12-1.83, P=0.04) were non-genetic independent risk factors for the occurrence of IS. Analysis of the association between the genetic polymorphisms and the risk of IS showed that the AA genotype at rs4244285 of the CYP2C19 gene, the AG genotype and A allele at rs4986893 of the CYP2C19 gene, and the GG genotype and G allele at rs776746 of the CYP3A5 gene were significantly associated with IS. Under the recessive/additive model, dominant model and dominant/additive model, polymorphisms of the rs4244285, rs4986893 and rs776746 loci were also significantly associated with the IS. Conclusion TC, LDL-C, Apo-A1, Apo-B and Hcy can all affect the occurrence of IS, and CYP2C19 and CYP3A5 gene polymorphisms are closely associated with the IS. Above finding has confirmed that the CYP450 gene polymorphisms can increase the risk of IS, which may provide a reference for the clinical diagnosis.

    细胞色素P450基因多态性缺血性脑卒中发病风险

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    Miller-Dieker综合征胎儿1例的产前遗传学分析

    王凤阳祁娜王涛高越...
    505-510页
    查看更多>>摘要：目的 探讨1例超声提示双侧侧脑室增宽胎儿的遗传学病因。 方法 采集胎儿的脐带血样及其父母的外周血样，对胎儿进行染色体核型分析，对胎儿及其父母应用微阵列比较基因组杂交(aCGH)技术进行拷贝数变异(CNV)分析，用qPCR技术验证候选致病CNV，用Goldeneye DNA身份鉴定系统确认生物学关系。 结果 胎儿的染色体核型未见异常。aCGH分析结果提示其17p13.3区存在1.16 Mb的杂合缺失(1615572_2777617)×1，部分覆盖Miller-Dieker综合征(MDS)核心区域，同时17p12区域还存在1.33 Mb的杂合缺失(14111772_15442066)×1，该缺失可导致遗传性压力易感性周围神经病(HNPP)。孕妇外周血17p12区存在1.33 Mb杂合缺失(14111772_15442066)×1。胎儿父亲外周血检测未见异常。qPCR分析结果提示胎儿脐带血17p13.3和17p12区域以及孕妇外周血17p12区域基因表达量约为正常对照的1/2。亲缘关系鉴定结果显示胎儿父母确为其生物学父母，胎儿父母选择继续妊娠。 结论 胎儿确诊为新发变异MDS，脑室增宽可能是MDS胎儿产前超声的一个重要指标。 Objective To explore the genetic basis for fetus with bilateral lateral ventriculomegaly. Methods Fetus umbilical cord blood and peripheral blood samples of its parents were collected. The fetus was subjected to chromosomal karyotyping, whilst the fetus and its parents were subjected to array comparative genomic hybridization (aCGH). The candidate copy number variation (CNV) were verified by qPCR, Application goldeneye DNA identification system was used to confirm the parental relationship. Results The fetus was found to have a normal karyotype. aCGH analysis indicated that it has carried a 1.16 Mb deletion at 17p13.3, which partially overlapped with the critical region of Miller-Dieker syndrome (MDS), in addition with a 1.33 Mb deletion at 17p12 region, which is associated with hereditary stress-susceptible peripheral neuropathy (HNPP). Its mother was also found to harbor the 1.33 Mb deletion at 17p12. qPCR analysis confirmed that the expression levels of genes from the 17p13.3 and 17p12 regions were about the half of that in the normal control, as well as the maternal peripheral blood sample. Parental relationship was confirmed between the fetus and its parents. Following genetic counseling, the parents has chosen to continue with the pregnancy. Conclusion The fetus was diagnosed with Miller-Dieker syndrome due to the de novo deletion at 17p13.3. Ventriculomegaly may be an important indicator for prenatal ultrasonography in fetuses with MDS.

    Miller-Dieker综合征PAFAH1B1基因遗传性压力易感性周围神经病

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    产前诊断20号三体与单亲二体嵌合体1例

    赵军红吴庆华侯雅勤孔祥东...
    510-511页
    查看更多>>摘要：孕妇 27岁，G1P0，孕18+2周因"高通量无创产前筛查提示20号染色体数目偏多"就诊。此次妊娠为自然受孕，夫妻双方系非近亲结婚，外观及智力均无异常，无明显毒物及放射线接触史，否认遗传病家族史。本研究通过了郑州大学第一附属医院医学伦理委员会审查(KS-2018-KY-36)，孕妇已签署临床研究知情同意书。
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    46，XX，t(5；6；18)(q33；q25；q12)复杂染色体重排携带者产前诊断1例

    琚端史云芳孟凡荣张颖...
    512页
    查看更多>>摘要：患者 女，30岁，G6P0，因"染色体异常且有复发性流产史"就诊于本中心。曾自然流产2次，孕8+周胚胎停育3次，于外院进行外周血染色体核型分析提示染色体平衡易位，未见报告。身高160 cm，体质量60 kg，表型及智力均正常，第二性征和外生殖器均无异常。本次妊娠为自然受孕，孕21周，胎儿发育与孕周相符，超声未见异常。否认吸烟、酗酒及有毒有害放射性物质接触史。予羊膜腔穿刺进行羊水核型分析与拷贝数变异测序，同时复检患者外周血染色体核型，结果提示患者核型为46，XX，t(5；6；18)(q33；q25；q12)(图1A)，胎儿核型为46，XN，t(6；18)(q26；q21.2)(图1B)且无致病性拷贝数变异。经充分遗传咨询后患者选择继续妊娠，孕39周顺产1女婴，体质量3 080 g，身长50 cm，随访至今未见异常。本研究通过了医院医学伦理委员会的审查(IRB2023-WZ-031)，患者及其家属均已签署临床研究知情同意书。
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