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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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    MEF2C基因变异所致NEDHSIL患儿2例的临床及遗传学分析

    闫露露庄丹燕屠友权张玉鑫...
    1252-1256页
    查看更多>>摘要：目的 探讨2例NEDHSIL患儿的临床特征及其遗传学病因，为其遗传咨询提供依据。 方法 选取2021年10月15日于宁波市妇女儿童医院就诊的2例患儿为研究对象。采用全外显子组测序(WES)技术对患儿进行检测，针对可疑变异进行Sanger测序验证与致病性分析。 结果 患儿1携带MEF2C基因c.138delC(p.Ile47Serfs*42)杂合新发变异，患儿2携带MEF2C基因c.833del(p.L278*)杂合新发变异。根据美国医学遗传学与基因组学学会(ACMG)相关指南，MEF2C基因c.138delC和c.833del变异均评为致病性变异(PVS1＋PS2＋PM2_Supporting)。 结论 MEF2C基因c.138delC和c.833del变异可能分别为2例NEDHSIL患儿的致病原因，丰富了MEF2C基因的变异谱，为家系的遗传咨询提供了依据。 Objective To explore the clinical characteristics and genetic etiology for two children with Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language (MEDHSIL). Methods Two children who had visited the Ningbo Women and Children's Hospital on October 15, 2021 were selected as the study subjects. Whole exome sequencing (WES) was carried out for both patients. Candidate variants were verified by Sanger sequencing of their family members. Results The two children were respectively found to harbor a heterozygous c. 138delC (p.Ile47Serfs*42) variant and a c. 833del (p.L278*) variant of the MEF2C gene. Neither variant was detected in their parents. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PVS1+ PS2+ PM2_Supporting). Conclusion The c. 138delC and c. 833del variants of the MEF2C gene probably underlay the pathogenesis of MEDHSIL in the two children. Above findings have enriched the mutational spectrum of the MEF2C gene and enabled genetic counseling for their families.

    NEDHSIL全外显子组测序MEF2C基因

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    FANCB基因半合子变异致多发畸形胎儿1例的分析

    高璐俞冬熠刘娜徐臻...
    1257-1262页
    查看更多>>摘要：目的 对1个产前肢体畸形合并心脏发育异常胎儿的家系进行研究，明确其遗传学病因，提高对FANCB基因致病变异导致胎儿多发畸形遗传病因和机制的认识。 方法 选取2021年4月30日于山东省妇幼保健院就诊的1个产前超声提示胎儿发育异常的家系为研究对象。采集该家系相关临床资料，对胎儿进行全外显子组测序(WES)，应用Sanger测序进行家系验证并分析候选变异致病性，对女性成员进行X染色体失活偏倚检测。 结果 胎儿孕龄为11＋周，产前超声提示脑膜脑膨出、双侧桡骨缺失、唇裂可能、大动脉发育异常及单脐动脉。WES检测提示胎儿携带FANCB基因c.1162del(p.Y388Tfs*7)半合子变异，Sanger测序验证该变异系母源遗传，根据美国医学遗传学与基因组学学会(ACMG)与ClinGen制订的相关指南，该变异判读为致病性变异(PVS1＋PM2_Supporting＋PP4)。X染色体失活偏倚检测提示孕妇及其母亲的X染色体均完全失活。 结论 FANCB基因c.1162del(p.Y388Tfs*7)半合子变异可能为本研究胎儿肢体畸形合并心脏发育异常的遗传学病因，该基因的致病变异类型与表型之间具有一定的对应关系。 Objective To explore the genetic basis for a fetus with limb abnormality and cardiac malformation. Methods Clinical data of a fetus diagnosed at the Shandong Provincial Maternal and Child Health Care Hospital on April 30th, 2021 was collected. Whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. X-inactivation analysis was carried out for the female members of its family. Results The fetus was found to have meningoencephalocele, absence of bilateral radii, cleft lip, abnormal great arteries, and single umbilical artery at the gestational age of 11+ weeks. Sequencing revealed that the fetus has harbored a hemizygous c. 1162del (p.Y388Tfs*7) variant of the FANCB gene, which was maternally inherited. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and ClinGen, the variant was classified as pathogenic (PVS1+ PM2_Supporting+ PP4). X-inactivation analysis has revealed complete skewed X-inactivation in the pregnant woman and her mother. Conclusion The hemizygous c. 1162del (p.Y388Tfs*7) variant of the FANCB gene probably underlay the multiple malformations in this fetus.

    肢体畸形FANCB基因X染色体失活偏倚全外显子组测序胎儿

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    COL4A5基因剪接变异致Alport综合征患者1例的遗传学分析及体外验证

    梁磊蔡泽宇吴昊天孟海霞...
    1263-1269页
    查看更多>>摘要：目的 探讨1例Alport综合征(AS)患者的遗传学特征并验证其存在的剪接变异。 方法 选取2021年1月8日因"体检发现尿蛋白3＋、尿潜血3＋"就诊于内蒙古医科大学附属医院肾脏内科的1例AS患者作为研究对象，收集患者临床资料。抽取患者及其父母的外周血样本，提取基因组DNA，利用全外显子组测序及Sanger测序确定基因变异位点，应用mRNA异常剪接体外验证实验研究变异对转录产物的影响。应用生物学软件分析变异位点的氨基酸保守性并模拟胶原蛋白Ⅳ模型，分析变异蛋白的三维结果。对患者肾组织进行免疫荧光与免疫组织化学检查，确认是否存在AS肾脏损伤。 结果 患者为21岁男性，门诊尿常规检查显示24 h尿蛋白3.53 g/24 h(大量蛋白尿)，血尿酸491 μmol/L(高尿酸血症)。基因测序结果显示患者COL4A5基因存在剪接变异c.835-9T>A，患者父母未见该变异。体外实验结果显示c.835-9T>A(p.279_297del)导致COL4A5基因mRNA的第15外显子缺失57 bp，造成第279~297位氨基酸残基缺失，影响COL4A5基因编码的α5链的二级结构的稳定性。受损的氨基酸在不同物种中高度进化保守。同源建模显示突变的α5链参与的Col-Ⅳ三聚化可以完成，但三维结构变形严重。免疫荧光结果诊断为AS肾脏损伤。根据美国医学遗传学与基因组学学会相关变异评级指南，c.835-9T>A评级为可能致病性变异(PVS1_Moderate ＋PS3_Moderate＋PM2_Supporting＋PS2＋PP3＋PP4)。 结论 COL4A5：c.835-9T>A考虑是AS患者致病的原因，体外实验证实为剪接变异。通过肾脏组织病理学检查为该变异的致病性提供了体内证据，并拓展了COL4A5基因的变异谱。 Objective To explore the genetic basis for a patient with Alport syndrome (AS) and confirm the existence of a splicing variant. Methods An AS patient diagnosed at the Affiliated Hospital of Inner Mongolia Medical University on January 8, 2021 for significant proteinuria and occult hematuria was selected as the study subject. Clinical data was collected. Peripheral blood samples were collected for the extraction of genomic DNA. Whole exome sequencing and Sanger sequencing were carried out to identify potential genetic variants. An in vitro experiment was also conducted to verify the abnormal mRNA splicing. Bioinformatic software was used to analyze the conservation of amino acids of the variant sites and simulate the 3D structure of the variant collagen IV protein. Immunofluorescence and immunohistochemistry were carried out on renal tissues from the patient to confirm the presence of AS kidney injury. Results The patient, a 21-year-old male, had a 24-hour urine protein of 3.53 g/24 h, which fulfilled the diagnostic criteria for proteinuria. His blood uric acid has also increased to 491 μmol/L. DNA sequencing revealed that he has harbored a c. 835-9T>A splice variant of the COL4A5 gene, which was not found in either of his parents. In vitro experiment confirmed that the variant has removed 57 bp from the exon 15 of the mRNA of the COL4A5 gene. The deletion may cause loss of amino acid residues from positions 279 to 297, which in turn may affect the stability of the secondary structure of the α5 chain encoded by the COL4A5 gene. The amino acids are conserved across various species. The result of homology modeling indicated that the trimerization of Col-IV with the mutated α5 chain could be achieved, however, the 3D structure was severely distorted. The AS kidney damage was confirmed through immunofluorescence assays. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 835-9T>A variant was classified as likely pathogenic (PVS1_Moderate+ PS3_Moderate+ PM2_Supporting+ PS2+ PP3+ PP4). Conclusion The c. 835-9T>A variant of theCOL4A5 gene probably underlay the AS in this patient. In vitro experiment has confirmed the abnormal splicing caused by the variant. Histopathological examination of the kidney tissue has provided in vivo evidence for its pathogenicity. Above finding has expanded the mutational spectrum of the COL4A5 gene.

    Alport综合征COL4A5基因剪接变异成人

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    X连锁显性遗传型Alport肾病综合征患儿1例的临床及遗传学分析

    常甜韩智刘肖王盼盼...
    1270-1274页
    查看更多>>摘要：目的 探讨1例X连锁显性遗传Alport综合征(XLAS)患儿的临床特征及基因变异特点。 方法 选取2019年5月至郑州大学第一附属医院肾内科就诊的1例XLAS患儿为研究对象。收集患儿的临床资料。应用二代测序(NGS)对患者进行基因检测，针对候选致病变异，进行Sanger测序家系验证。 结果 患为12岁男性，儿主要临床表现为肉眼血尿、蛋白尿、肾病综合征，呈渐进性肾损害，伴听力下降，肾穿刺病理活组织检查提示肾小球基底膜弥散厚薄不均。基因检测结果提示患儿及其母亲携带COL4A5基因c.2632G>A(p.G878R)半合子变异，其父亲及弟弟该位点为野生型。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评估为致病性变异(PS1＋PM1＋PM2_Supporting＋PP3) 结论 母源性COL4A5基因c.2632G>A(p.G878R)变异可能为该XLAS患儿的遗传学病因。本研究丰富了COL4A5基因的变异谱。 Objective To investigate the clinical features and genetic variant of a child with X-linked dominant Alport syndrome (XLAS). Methods A child who had presented at the First Affiliated Hospital of Zhengzhou University in May 2019 was selected as the study subject. Clinical data of the child was collected. Next generation sequencing (NGS) was carried out for the child. Candidate variants were validated by Sanger sequencing of his family members. Results The child, a 12-year-old boy, had mainly manifested gross hematuria, proteinuria, nephrotic syndrome, and progressive renal impairment in conjunct with hearing loss. Kidney biopsy has revealed uneven glomerular basement membrane thickness. DNA sequencing revealed that the child and his mother have both carried a heterozygous c. 2632G>A (p.G878R) variant of theCOL4A5 gene, for which his father and brother were of the wild type. This variant was unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was classified as pathogenic (PS1+ PM1+ PM2_Supporting+ PP3). Conclusion The maternally derived hemizygous c. 2632G>A (p.G878R) variant of theCOL4A5 gene probably underlay the XLAS in this child. Above finding has enriched the mutational spectrum of the COL4A5 gene.

    Alport综合征X连锁显性遗传COL4A5基因基因变异

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    ATP6V0A4基因变异致原发性远端肾小管酸中毒患儿1例的临床特征及遗传学分析

    李玛丽胡姝雯刘超宋娜...
    1275-1279页
    查看更多>>摘要：目的 分析1例原发性远端肾小管酸中毒(dRTA)患儿的临床及遗传学特征。 方法 选取2021年4月因"食纳差10 d，哭闹2 d"就诊于西安市儿童医院的1例原发性dRTA患儿作为研究对象，收集患儿的临床资料。应用全外显子组测序及Sanger测序进行变异分析及家系验证。 结果 患儿为1月18日龄男性，临床主要表现为食纳差、烦躁哭闹、体重不增及脱水。患儿实验室检查提示代谢性酸中毒、电解质紊乱(高氯、低钾)、反常性碱性尿及贫血；泌尿系彩色多普勒超声提示双肾髓质钙盐沉积。基因检测发现患儿ATP6V0A4基因存在父源性c.1363dupA(p.M455NfsX14)和母源性c.2257C>T(p.Q753X)复合杂合变异。根据美国医学遗传学与基因组学学会相关变异标准与指南，c.1363dupA(p.M455NfsX14)评级为致病性变异(PVS1＋PM3＋PM2_Supporting)，c.2257C>T(p.Q753X)评级为致病性变异(PVS1＋PM3＋PM2_Supporting)。 结论 ATP6V0A4基因c.1363dupA(p.M455NfsX14)和c.2257C>T(p.Q753X)变异考虑是患儿致病的原因。c.2257C>T(p.Q753X)变异的发现拓展了ATP6V0A4基因的变异谱。 Objective To explore the clinical features and genetic etiology of a patient with primary distal renal tubular acidosis (dRTA). Methods A child who was diagnosed with primary dRTA at the Xi'an Children′s Hospital in April 2021 due to poor appetite and persistent crying was selected as the study subject. Clinical data of the patient was collected. Whole exome sequencing (WES) was carried out for the child. Candidate variants were validated by Sanger sequencing of his family members. Results The child, a 1-month-and-18-day male, had featured poor appetite, persistent crying, poor weight gain and dehydration. Laboratory examination has suggested metabolic acidosis, hyperchloremia, hypokalemia, abnormal alkaline urine and anemia. Ultrasonographic examination of the urinary system revealed calcium deposition in renal medulla. DNA sequencing revealed that he has harbored compound heterozygous variants of the ATP6V0A4 gene, namely c. 1363dupA (p.M455NfsX14) and c. 2257C>T (p.Q753X), which were respectively inherited from his father and mother. Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were classified as pathogenic (PVS1+ PM3+ PM2_Supporting). Conclusion The compound heterozygous variants of c. 1363dupA (p.M455NfsX14) and c. 2257C>T (p.Q753X) of theATP6V0A4 gene probably underlay the pathogenesis of primary dRTA in this patient. Discovery of the c. 2257C>T (p.Q753X) variant has expanded the mutational spectrum of theATP6V0A4 gene.

    酸中毒,肾小管性ATP6V0A4基因基因变异代谢性酸中毒低钾血症儿童

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    Raynaud-Claes综合征患儿1例的 CLCN4基因变异分析

    李林飞罗淑颖梅世月尚清...
    1280-1283页
    查看更多>>摘要：目的 分析1例CLCN4基因变异所致Raynaud-Claes综合征(RCS)患儿的临床表型和基因变异情况，为该病的诊断提供参考。 方法 选取2022年8月因"语言与运动较同龄儿落后"于郑州大学附属儿童医院康复医学科门诊的1例RCS男性患儿为研究对象。采集患儿临床资料，应用目标捕获高通量测序和Sanger测序技术对患儿及其父母进行基因变异检测，并对候选变异进行致病性分析。 结果 患儿为4岁4个月男性，表现为全面发育迟缓、言语障碍、特殊面容及行为异常。基因检测结果提示患儿CLCN4基因存在c.1174C>T(p.Gln392Ter)半合子变异，其父母均未携带该变异，提示为新发变异。根据美国医学遗传学与基因组学学会(ACMG)相关指南，该变异被评定为致病性变异(PVS1＋PS2＋PM2_Supporting)。 结论 CLCN4基因c.1174C>T(p.Gln392Ter)新发变异可能是本研究患儿的遗传致病原因，该变异的发现进一步扩大了RCS的致病基因变异谱，为该家系遗传咨询及产前诊断提供依据。 Objective To analyze the clinical phenotype and genetic variant in a child with Raynaud-Claes syndrome (RCS). Methods A child who was diagnosed with RCS at the Children′s Hospital Affiliated to Zhengzhou University for delayed language and motor development in August 2022 was selected as the study subject. Clinical data of the child were collected, and potential genetic variant was detected by next-generation sequencing and Sanger sequencing. The pathogenicity of the candidate variant was analyzed. Results The child, a 4-year-and-4-month-old male, has manifested global developmental delay, speech disorders, special facial features and behavioral abnormalities. Genetic testing revealed that he has harbored a hemizygous c. 1174C>T (p.Gln392Ter) variant of theCLCN4 gene, which was not detected in either of his parents. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+ PS2+ PM2_Supporting). Conclusion The c. 1174C>T (p.Gln392Ter) variant of theCLCN4 gene probably underlay the PCS in this child. Above finding has expanded the mutational spectrum of the CLCN4 gene and enabled genetic counseling and prenatal diagnosis for his family.

    Raynaud-Claes综合征CLCN4基因新发变异

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    MAGEL2基因杂合变异致婴儿期Schaaf-Yang综合征1例的临床特征与遗传学分析

    龚姣娥江志胡文静廖红梅...
    1284-1287页
    查看更多>>摘要：目的 探讨1例Schaaf-Yang综合征(SYS)患儿的诊疗过程与遗传学分析。 方法 以2020年6月10日就诊于湖南省儿童医院的1例SYS患儿作为研究对象。对患儿及其父母进行全外显子组检测，对候选变异进行Sanger测序家系验证。通过预测野生型与变异型蛋白的结构来分析其危害性。 结果 基因检测提示患儿携带MAGEL2基因杂合移码变异c.1908delG(p.R637Gfs*65)，其父母该位点均为野生型，提示为新发。该变异未被相关公共数据库收录，既往未见文献报道。该变异可造成MAGEL2蛋白仅保留部分脯氨酸结构域，导致蛋白功能破坏或下调。 结论 MAGEL2基因的c.1908delG(p.R637Gfs*65)新发变异可能是本研究患儿的遗传学病因，结合其临床特征诊断为SYS。上述发现丰富了MAGEL2基因的变异谱。 Objective To explore the diagnosis, treatment and genetic analysis of an infant with Schaaf-Yang syndrome (SYS). Methods An infant suspected for SYS at the Hunan Provincial Children′s Hospital on June 10, 2022 was subjected to trio-whole exome sequencing, and Sanger sequencing was used to verify the candidate variant. Structure of the wild-type and variant proteins was constructed to analyze the potential hazard. Results The infant was found to harbor a heterozygous frameshifting variant of c. 1908delG (p.R637Gfs*65) of the MAGEL2 gene, which was found in neither of his parents. The variant has not been recorded by the public databases, and no relevant literature was retrieved. As the result of the variant, the MAGEL2 protein only retained part of its proline domain, which may lead to destruction and/or down-regulation of its function. Conclusion The c. 1908delG (p.R637Gfs*65) variant of the MAGEL2 gene probably underlay the pathogenesis in this child. Combined with his clinical characteristics, the child was diagnosed with SYS. Above finding has also enriched the mutational spectrum of the MAGEL2 gene.

    Schaaf-Yang综合征MAGEL2基因印记基因Prader-Willi综合征

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    PIGW基因纯合变异致发育障碍合并癫痫发作患儿1例的遗传学分析

    曾洁群田杨陈连凤蔡佳濠...
    1288-1291页
    查看更多>>摘要：目的 探讨1例发育障碍合并癫痫发作患儿的遗传学病因。 方法 选取2022年7月于广州市妇女儿童医疗中心神经内科就诊的1例发育障碍合并癫痫发作患儿为研究对象。回顾性分析患儿相关临床资料，对患儿进行全外显子组测序(WES)，对候选变异进行Sanger测序验证与致病性分析。 结果 患儿为3岁女性，壮族人，主要表现为发育障碍合并癫痫发作，康复治疗无效。WES显示患儿携带PIGW基因c.821T>C(p.Leu274Pro)纯合错义变异，Sanger测序证实患儿父母与姐姐均携带PIGW基因c.821T>C(p.Leu274Pro)杂合错义变异，提示该变异遗传自父母。根据ACMG相关指南，该变异被评定为临床意义不明。 结论 PIGW基因c.821T>C(p.Leu274Pro)纯合变异可能是本研究患儿的遗传学病因，进一步丰富了PIGW基因变异谱。 Objective To explore the genetic basis for a child featuring global developmental disorder with epilepsy. Methods A child who had presented at Guangzhou Women and Children′s Medical Center in July 2022 was selected as the study subject. Clinical data was collected. Potential variant was detected by whole exome sequencing (WES). Candidate variant was validated by Sanger sequencing and bioinformatic analysis. Results The child, a three-year-old ethnic Zhuang Chinese girl, had presented with global developmental disorder and epilepsy, for which rehabilitation therapy was ineffective. Genetic testing revealed that she has harbored a homozygous c. 821T>C (p.Leu274Pro) missense variant of thePIGW gene, for which both of her parents and sister were heterozygous carriers. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as variant of uncertain significance. Conclusion The homozygous c. 821T>C (p.Leu274Pro) variant of thePIGW gene probably underlay the onset of disease in this child. Above finding has enriched the mutational spectrum of the PIGW gene.

    发育障碍癫痫PIGW基因

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    ORC6基因变异致Meier-Gorlin综合征患儿1例的遗传学分析

    王莉莉王凤云王晓艳陈临琪...
    1292-1295页
    查看更多>>摘要：目的 分析1例ORC6基因纯合变异所致Meier-Gorlin综合征(MGS)患儿的遗传学特征。 方法 选取2019年3月25日因"自幼生长迟缓"就诊于苏州大学附属儿童医院的1例MGS患儿作为研究对象，收集患儿的临床资料。应用全外显子组测序确认患儿候选位点，Sanger验证确认变异位点并进行致病性分析。 结果 患儿为8岁3个月男性，临床表现为身材矮小、双耳均小、双侧隐睾术后、髌骨发育不良。患儿父母为表兄妹婚配。患儿ORC6基因存在c.712A>T(p.K238*)纯合错义变异，导致氨基酸翻译提前终止。Sanger验证其父母为该变异携带者。根据美国医学遗传学与基因组学学会相关变异指南，c.712A>T(p.K238*)评级为致病性变异(PVS1_Moderate＋PM2_Supporting＋PM3＋PP3＋PP4)。 结论 c.712A>T(p.K238*)考虑是MGS患儿致病的原因，为患儿的确诊提供帮助。 Objective To analyze the genetic characteristics of a child with Meier-Gorlin syndrome (MGS) due to a homozygous variant of the ORC6 gene. Methods A child who was admitted to the Children′s Hospital Affiliated to Soochow University on March 25, 2019 due to growth retardation was selected as the study subject. Clinical data of the child was collected. Whole exome sequencing was carried out for the child. Candidate variant was validated by Sanger sequencing and bioinformatic analysis. Results The child, a 8-year-and-3-month-old male, has featured short stature, small ears, bilateral cryptorchidism and patellar dysplasia. His parents were of first cousins. The child was found to harbor a homozygous c. 712A>T (p.K238*) missense variant of theORC6 gene, which may lead to premature termination of protein translation. Sanger sequencing confirmed that both of his parents were heterozygous carriers. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was classified as pathogenic (PVS1_Moderate+ PM2_Supporting+ PM3+ PP3+ PP4). Conclusion The homozygous c. 712A>T (p.K238*) variant probably underlay the MGS in this child.

    遗传性疾病,先天性矮小症ORC6基因Meier-Gorlin综合征儿童

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    联合应用多种遗传学方法鉴定1例嵌合型胎儿微小额外标记染色体

    卢静钿卢建秦红叶夏...
    1296-1300页
    查看更多>>摘要：目的 联合应用染色体微阵列分析(CMA)、荧光原位杂交(FISH)和染色体核型分析对1例嵌合型微小额外标记染色体(sSMC)进行鉴定。 方法 以2022年深圳市龙华区妇幼保健院无创产前检测(NIPT)提示胎儿染色体4q12-4q13.1区存在8.75 Mb重复的1例孕妇作为研究对象，采集羊水样本与夫妇双方的外周血样进行染色体G显带核型分析，用CMA鉴定sSMC的来源和大小，之后用FISH对羊水中sSMC的嵌合比例进行进一步的确定。 结果 孕妇外周血G显带染色体核型为46，XX，其丈夫为46，XY，inv(9)(p12q12)，胎儿为47，XY，inv(9)(p12q12)pat，＋mar[75]/46，XY，inv(9)(p12q12)pat[25]。羊水CMA检测结果为arr[hg19]4p11q13.1(48978053_63145931)×3，并未显示嵌合。FISH检测经培养的分裂间期的羊水细胞中59%包含3个4号染色体的着丝粒信号，复抽羊水检查，有65%的分裂间期羊水细胞包含3个4号染色体着丝粒信号，证实羊水为三体嵌合体。 结论 结构异常合并嵌合性的sSMC需要在传统染色体核型分析的基础上结合其他检测技术进行精确的鉴定，为患者提供更准确的遗传咨询。 Objective To delineate the origin and content of a mosaicism small supernumerary marker chromosome (sSMC) in a fetus with combined chromosomal karyotyping, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH). Methods The fetus of a 31-year-old pregnant woman who had presented at the Maternal and Child Health Care Hospital of Longhua District of Shenzhen City in 2022 was selected as the study subject. Non-invasive prenatal testing suggested that the fetus has harbored a 8.75 Mb duplication in 4q12q13.1. With informed consent, amniotic fluid and peripheral blood samples were taken from the couple for chromosomal karyotyping analysis. The origin and content of a sSMC was identified by CMA, and its proportion in amniotic fluid was determined with a FISH assay. Results The karyotypes of the pregnant woman, her husband and the fetus were respectively determined as 46, XX, 46, XY, inv(9)(p12q12), and 47, XY, inv(9)(p12q12)pat, + mar[75]/ 46, XY, inv(9)(p12q12)pat[25]. CMA test of the amniotic fluid sample was arr[hg19]4p11q13.1(48978053_63145931)×3, which revealed no mosaicism. However, FISH analysis showed that 59% of interphase cells from the cultured amniotic fluid sample had contained three signals for the centromere of chromosome 4, whilst 65% of interphase cells from the re-sampled amniotic fluid had three such signals, which confirmed the existence of trisomy 8 mosaicism. Conclusion Chromosomal structural abnormality combined with mosaicism can be delineated with combined chromosomal karyotyping and molecular techniques such as FISH and CMA, which has enabled more accurate counseling for the family.

    微小额外标记染色体染色体结构异常染色体核型染色体微阵列分析荧光原位杂交

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