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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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    孤独症谱系障碍合并先天性心脏病患儿1例的 NSD1基因变异分析

    尹恒邱忠清李童童陈娅君...
    701-705页
    查看更多>>摘要：目的 探讨1例孤独症谱系障碍(ASD)合并先天性心脏病(CHD)患儿的临床特征与遗传学病因。 方法 选取2021年4月13日于成都市第三人民医院就诊的1例ASD合并CHD患儿为研究对象。收集患儿临床资料，采集患儿及其父母外周静脉血样，应用全外显子组测序(WES)对患儿进行基因检测，使用GTX遗传分析系统对WES数据进行分析，筛选出ASD候选致病基因。进一步采用Sanger测序进行家系验证，并对候选变异进行生物信息学分析。利用实时荧光定量PCR(qPCR)技术，检测本研究患儿与3例正常同龄儿童和5例其他ASD患儿NSD1基因mRNA相对表达量的差异。 结果 患儿为男性，8岁，主要临床表现为ASD、智力低下及CHD。WES数据经GTX遗传分析系统分析，NSD1被筛选为该本研究患儿ASD候选致病基因，其NSD1基因存在c.3385+2T>C杂合变异，Sanger测序结果显示，患儿父母均未携带该变异，提示该变异为新发变异。生物信息学分析：NSD1基因c.3385+2T>C变异在ESP、1000 Genomes及ExAC等数据库中均未见收载；采取Mutation Taster在线软件对该变异有害性分析结果显示，提示为可能有害变异；根据美国医学遗传学与基因组学学会(ACMG)指南，该变异被评级为致病性变异。qPCR检测结果显示，与3例正常同龄儿童相比，本研究患儿和其他5例确诊ASD患儿的NSD1基因mRNA相对表达量均显著降低，并且差异有统计学意义(P<0.001)。 结论 NSD1基因c.3385+2T>C变异可导致其mRNA表达水平显著降低，与ASD具有一定关联，可能是本研究ASD患儿的遗传学病因，进一步拓展了NSD1基因变异谱。 Objective To explore the clinical characteristics and genetic basis of a child with autism spectrum disorder (ASD) in conjunct with congenital heart disease (CHD). Methods A child who was hospitalized at the Third People′s Hospital of Chengdu on April 13, 2021 was selected as the study subject. Clinical data of the child were collected. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). A GTX genetic analysis system was used to analyze the WES data and screen candidate variants for ASD. Candidate variant was verified by Sanger sequencing and bioinformatics analysis. Real-time fluorescent quantitative PCR (qPCR) was carried out to compare the expression of mRNA of the NSD1 gene between this child and 3 healthy controls and 5 other children with ASD. Results The patient, an 8-year-old male, has manifested with ASD, mental retardation and CHD. WES analysis revealed that he has harbored a heterozygous c. 3385+ 2T>C variant in theNSD1 gene, which may affect the function of its protein product. Sanger sequencing showed that neither of his parent has carried the same variant. By bioinformatic analysis, the variant has not been recorded in the ESP, 1000 Genomes and ExAC databases. Analysis with Mutation Taster online software indicated it to be disease causing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be pathogenic. By qPCR analysis, the expression level of mRNA of the NSD1 gene in this child and 5 other children with ASD was significantly lower than that of the healthy controls (P < 0.001). Conclusion The c. 3385+ 2T>C variant of theNSD1 gene can significantly reduce its expression, which may predispose to ASD. Above finding has enriched the mutational spectrum the NSD1 gene.

    孤独症谱系障碍NSD1基因遗传变异心脏病,先天性智力障碍儿童

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    颅额鼻综合征患者1例的临床及遗传学分析

    金娟雷俞蒲茜余蕾...
    706-710页
    查看更多>>摘要：目的 探讨1例颅额鼻综合征(CNFS)患者的临床特征及遗传学病因。 方法 选取2021年11月13日于贵阳市妇幼保健院就诊的1例CNFS患者为研究对象。收集患者的临床资料，抽取患者及其父母的外周静脉血样，进行家系全外显子组测序(trio-WES)与Sanger测序验证，并对候选变异进行生物信息学分析。 结果 患者为15岁女性，以前额膨凸、眼距与鼻背过宽、双鼻尖为主要临床表现。基因检测结果提示其携带EFNB1基因c.473T>C(p.M158T)杂合错义变异，其父母均未携带该变异。生物信息学分析：EFNB1基因c.473T>C(p.M158T)变异在HGMD及ClinVar数据库中未见收录，在1000 Genomes、ExAC、gnomAD及神州基因组数据云等数据库中均未见人群携带频率收录；经REVEL在线软件预测，该变异对基因或基因产物可造成有害影响；经UGENE软件分析，该变异位点所编码的氨基酸在不同物种间高度保守；经AlphaFold2软件进行3D建模显示，该变异可能影响Ephrin-B1蛋白的结构与功能。根据美国医学遗传学与基因组学学会(ACMG)指南与临床基因组资源中心(ClinGen)的建议，该变异被评级为致病性变异。 结论 结合患者的临床特征与基因检测结果，确诊其为CNFS，EFNB1基因c.473T>C(p.M158T)杂合错义变异可能为该患者的遗传学病因。上述发现为其家系的遗传咨询和产前诊断提供了依据。 Objective To explore the clinical feature and genetic etiology of a patient with Craniofacial nasal syndrome (CNFS). Methods A patient with CNFS who had presented at the Guiyang Maternal and Child Health Care Hospital on November 13, 2021 was selected as the study subject. Clinical data of the patient were collected. Peripheral venous blood samples were collected from the patient and her parents and subjected to trio-whole exome sequencing (trio-WES). Candidate variants were verified by Sanger sequencing and bioinformatic analysis. Results The patient, a 15-year-old female, had predominantly featured forehead bulging, hypertelorism, wide nasal dorsum and bifid nasal tip. Genetic testing revealed that she has harbored a heterozygous missense c. 473T>C (p.M158T) variant of theEFNB1 gene, which was detected in either of her parents. By bioinformatic analysis, the variant has not been recorded in the HGMD and ClinVar databases, and no population frequency was recorded in the 1000 Genomes, ExAC, gnomAD and Shenzhou Genome Data Cloud databases. As predicted by the REVEL online software, the variant can confer deleterious effects on the gene or its product. Analysis using UGENE software showed the corresponding amino acid to be highly conserved among various species. Analysis with AlphaFold2 software suggested that the variant may affect the 3D structure and function of the Ephrin-B1 protein. Based on the American College of Medical Genetics and Genomics (ACMG) standards and guidelines and recommendation of Clinical Genome Resource (ClinGen), the variant was rated as pathogenic. Conclusion Combining the patient’s clinical features and genetic finding, the diagnosis of CNFS was confirmed. The heterozygous c. 473T>C (p.M158T) missense variant of theEFNB1 gene probably underlay the disease in this patient. Above finding has provided a basis for the genetic counseling and prenatal diagnosis for her family.

    颅额鼻综合征颅缝早闭EFNB1基因家系全外显子组测序

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    晚发型糖原贮积症Ⅱ型患儿1例的溶酶体酶活性分析及遗传学分析

    何甜甜江杰妮熊悦月俞丹...
    711-717页
    查看更多>>摘要：目的 探讨1例晚发型糖原贮积症Ⅱ型(LOPD)型患儿的临床特征、GAA基因变异特点及溶酶体酶α-葡萄糖苷酶(GAA)活性改变情况。 方法 收集2020年8月在四川大学华西第二医院临床确诊的1例GSDⅡ患儿的病历资料，采集患儿及其父母的外周血样，分别用于外周血白细胞、淋巴细胞分离及基因组DNA提取，检测2种细胞中加入GAA同工酶抑制剂阿卡波糖和不加抑制剂时溶酶体酶GAA的活性。同时收集20例健康受试者的外周血样，混合后分别分离白细胞与淋巴细胞，与患儿家系同批次进行GAA活性测定，作为正常参考值。基因组DNA用于神经肌肉病基因panel检测，并对候选变异进行Sanger测序验证和保守性分析。 结果 患儿为9岁女性，2岁11个月时发现语言运动发育落后，就诊时走路不稳、上台阶困难及明显脊柱侧弯，患儿血清肌酸激酶显著升高、肌电图异常，心脏彩色多普勒超声未见异常。基因检测发现其携带GAA基因c.1996dupG(p.A666Gfs*71)和c.701C>T(p.T234M)复合杂合变异。根据美国医学遗传学与基因组学学会相关指南，分别评级为致病变异(PVS1+PM2_Supporting +PM3)和可能致病变异(PM1+PM2_Supporting +PM3+PM5+PP3)。患儿、患儿父亲、母亲白细胞中GAA活性在不加抑制剂时分别为同批次正常值的76.1%、91.3%、95.6%，加入抑制剂时分别为同批次正常值的70.8%、112.9%、128.2%，白细胞中GAA活性在加入抑制剂后降低约6 ~ 9倍；患儿、患儿父亲、母亲淋巴细胞中GAA活性在不加抑制剂时分别为同批次正常值的68.3%、59.0%、59.5%，在加抑制剂时分别为同批次正常值的41.0%、89.5%、57.7%，淋巴细胞中GAA活性在加入抑制剂后降低约2 ~ 5倍。 结论 患儿被诊断为LOPD，其GAA基因的c.1996dupG和c.701C>T复合杂合变异可能是其遗传学病因。LOPD患儿GAA残余酶活性范围较宽，酶活性改变不典型，在诊断时不能仅依据酶活性检测，而需要结合临床表现、基因检测和酶活性检测进行综合诊断。 Objective To explore the clinical features, lysosomal enzymatic [acid α-glucosidase (GAA)] activities and genetic variants in a child with late-onset Pompe disease (LOPD). Methods Clinical data of a child who had presented at the Genetic Counseling Clinic of West China Second University Hospital in August 2020 was retrospectively analyzed. Blood samples were collected from the patient and her parents for the isolation of leukocytes and lymphocytes as well as DNA extraction. The activity of lysosomal enzyme GAA in leukocytes and lymphocytes was analyzed with or without addition of inhibitor of GAA isozyme. Potential variants in genes associated with neuromuscular disorders were analyzed, in addition with conservation of the variant sites and protein structure. The remaining samples from 20 individuals undergoing peripheral blood lymphocyte chromosomal karyotyping were mixed and used as the normal reference for the enzymatic activities. Results The child, a 9-year-old female, had featured delayed language and motor development from 2 years and 11 months. Physical examination revealed unstable walking, difficulty in going upstairs and obvious scoliosis. Her serum creatine kinase was significantly increased, along with abnormal electromyography, whilst no abnormality was found by cardiac ultrasound. Genetic testing revealed that she has harbored compound heterozygous variants of the GAA gene, namely c. 1996dupG (p.A666Gfs*71) (maternal) and c. 701C>T (p.T234M) (paternal). Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 1996dupG (p.A666Gfs*71) was rated as pathogenic (PVS1+ PM2_Supporting+ PM3), whilst the c. 701C>T (p.T234M) was rated as likely pathogenic (PM1+ PM2_Supporting+ PM3+ PM5+ PP3). The GAA in the leukocytes from the patient, her father and mother were respectively 76.1%, 91.3% and 95.6% of the normal value without the inhibitor, and 70.8%, 112.9% and 128.2% of the normal value with the inhibitor, whilst the activity of GAA in their leukocytes had decreased by 6 ~ 9 times after adding the inhibitor. GAA in lymphocytes of the patient, her father and mother were 68.3%, 59.0% and 59.5% of the normal value without the inhibitor, and 41.0%, 89.5% and 57.7% of the normal value with the inhibitor, the activity of GAA in lymphocytes has decreased by 2 ~ 5 times after adding the inhibitor. Conclusion The child was diagnosed with LOPD due to the c. 1996dupG and c. 701C>T compound heterozygous variants of theGAA gene. The residual activity of GAA among LOPD patients can range widely and the changes may be atypical. The diagnosis of LOPD should not be based solely on the results of enzymatic activity but combined clinical manifestation, genetic testing and measurement of enzymatic activity.

    糖原贮积症Ⅱ型酸性α-葡萄糖苷酶基因变异溶酶体酶活性分析儿童

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    戊二酸血症ⅡC型胎儿1例的临床表型及遗传学分析

    翟闪闪刘灵袁莉敏程国梅...
    718-722页
    查看更多>>摘要：目的 探讨1例戊二酸血症ⅡC型(GAⅡC)胎儿的临床表型及基因变异特征。 方法 选取2021年12月因"孕17周胎儿超声提示双肾体积增大并回声增强、羊水少"来郑州大学第三附属医院产前诊断中心就诊的1例32岁孕妇及其GAⅡC胎儿作为研究对象，收集孕妇的相关临床资料及胎儿的影像学检查信息。采集孕妇的羊水标本及孕妇夫妇的外周静脉血样本进行家系全外显子组测序，对候选变异进行Sanger测序家系验证，并利用低深度全基因组测序技术检测拷贝数变异(CNV)。 结果 胎儿孕18周超声提示双肾体积增大并回声增强、肾实质内裂隙样管状无回声、羊水过少。孕22周MRI提示双肾体积增大、T2信号异常均匀增高并DWI信号降低、双肺体积小并T2信号呈稍高信号。CNV检测结果未见异常。测序分析提示胎儿ETFDH基因存在母源性c.1285+1G>A及父源性c.343_344delTC复合杂合变异。根据美国医学遗传学与基因组学学会相关指南，判定二者均为致病变异(PVS1+PM2_Supporting+PS3_Supporting；PVS1+PM2_Supporting+PM3)。 结论 ETFDH基因c.1285+1G>A和c.343_344delTC复合杂合变异可能是患儿的遗传学病因，GAⅡC在胎儿期可表现为双侧肾脏体积增大并回声增强、羊水过少。上述发现丰富了ETFDH基因的变异谱。 Objective To explore the clinical phenotype and genetic variants of a fetus with Glutaracidemia type Ⅱ C (GA Ⅱ C). Methods Clinical data of a 32-year-old pregnant woman and her fetus with GA Ⅱ C diagnosed at the Third Affiliated Hospital of Zhengzhou University in December 2021 due to the enlargement and enhanced echo of the kidneys and oligohydramnios fluid at 17 weeks were analyzed retrospectively. Amniotic fluid sample of the fetus and peripheral blood samples of the couple were collected for whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing. Copy number variation (CNV) was detected by using low-coverage whole genome sequencing (CNV-seq). Results At 18 weeks′ gestation, ultrasound revealed that the fetus had enlargement and enhanced echo of the kidneys along with no echo of renal parenchymal tubular fissure and oligohydramnios. MRI at 22 weeks′ gestation confirmed that both kidneys were enlarged with uniformly increased abnormal T2 signal and decreased DWI signal. The volume of both lungs was small, with slightly higher T2 signal. No CNV was detected in the fetus. WES revealed that the fetus has harbored compound heterozygous variants of the ETFDH gene, namely c. 1285+ 1G>A and c. 343_344delTC, which were inherited from its father and mother, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+ PM2_Supporting+ PS3_Supporting PVS1+ PM2_Supporting+ PM3). Conclusion The c. 1285+ 1G>A and c. 343_344delTC compound heterozygous variants of theETFDH gene probably underlay the disease in this fetus. Type Ⅱ C glutaric acidemia may manifest as bilateral kidney enlargement with enhanced echo and oligohydramnios. Discovery of the c. 343_344delTC has enriched the spectrum of ETFDH gene variants.

    多酰基辅酶A脱氢酶缺乏戊二酸血症ⅡC型ETFDH基因全外显子组测序孕妇胎儿

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    Lesch-Nyhan综合征一个家系的遗传学分析

    王杜娟赵晶晶滕娟李文...
    723-726页
    查看更多>>摘要：目的 探讨1个Lesch-Nyhan综合征家系的遗传学病因。 方法 选取2022年2月10日在临沂市人民医院接受遗传咨询的1个Lesch-Nyhan综合征家系作为研究对象。收集先证者的临床资料及家族史，对先证者及其父母进行家系全外显子组测序(trio-WES)，对候选变异进行Sanger测序家系验证。 结果 先证者主要表现为精神及行为异常、运动发育迟缓和高尿酸血症，其表弟存在类似症状。基因检测发现先证者及其表弟均携带既往未见报道的HPRT1基因c.385-1G>C半合子变异，先证者母亲、外祖母、大姨、小姨、表妹均携带HPRT1基因c.385-1G>C杂合变异，家系中表型正常的男性该位点均为野生型，符合X连锁隐性遗传的特征。 结论 HPRT1基因c.385-1G>C半合子变异可能是该Lesch-Nyhan综合征家系的遗传学病因。 Objective To explore the genetic etiology for a Chinese pedigree affected with Lesch-Nyhan syndrome. Methods Members of the pedigree who had visited the Genetic Counseling Clinic of Linyi People′s Hospital on February 10, 2022 were selected as the study subjects. Clinical data and family history of the proband were collected, and trio-whole exome sequencing (trio-WES) was carried out for the proband and his parents. Candidate variants were verified by Sanger sequencing. Results Trio-WES revealed that both the proband and his cousin brother had harbored a hemizygous c. 385-1G>C variant in intron 4 of theHPRT1 gene, which was unreported previously. A heterozygous c. 385-1G>C variant of theHPRT1 gene was also found in the proband′s mother, grandmother, two aunts, and a female cousin, whilst all phenotypically normal males in his pedigree were found to have a wild type for the locus, which has conformed to an X-linked recessive inheritance. Conclusion The heterozygous c. 385-1G>C variant of theHPRT1 gene probably underlay the Lesch-Nyhan syndrome in this pedigree.

    高尿酸血症Lesch-Nyhan综合征HPRT1基因基因变异

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    罕见的17号染色体臂内反向插入一个家系的光学基因组图谱分析

    王昊杨扬杨南南汪燕...
    727-732页
    查看更多>>摘要：目的 应用光学基因组图谱(OGM)技术探讨1个罕见的17号染色体臂内反向插入家系的遗传学特征。 方法 选取2021年10月在杭州市妇产科医院产前诊断中心就诊的1例血清学筛查高风险孕妇及其家系成员作为研究对象。用染色体G显带核型分析、荧光原位杂交(FISH)、单核苷酸多态性微阵列(SNP array)、OGM等技术对该家系的17号染色体异常进行综合分析和验证。 结果 羊水染色体核型分析及SNP array检测提示胎儿染色体17q23q25区存在11 Mb重复。孕妇核型分析提示17号染色体结构异常，但SNP array检测未见异常，OGM检测提示其染色体17q23q25区存在臂内反向插入，经FISH检测确认。胎儿父亲核型未见异常。 结论 胎儿的染色体17q23q25区重复衍生自其母亲17号染色体的反向插入。OGM技术对于鉴定平衡性染色体结构异常具有一定的优势。 Objective To carry out optical genome mapping (OGM) for a Chinese pedigree with a rare paracentric reverse insertion of chromosome 17. Methods A high-risk pregnant woman identified at the Prenatal Diagnosis Center of Hangzhou Women′s Hospital in October 2021 and her family members were selected as the study subjects. Chromosome G banding analysis, fluorescence in situ hybridization (FISH), single nucleotide polymorphism array (SNP array) and OGM were applied to verify the balanced structural abnormality of chromosome 17 in the pedigree. Results Chromosomal karyotyping analysis and SNP array assay have identified a duplication of 17q23q25 in the fetus. Karyotyping analysis of the pregnant woman showed that the structure of chromosome 17 was abnormal, whilst SNP array has detected no abnormality. OGM revealed that the woman has carried a paracentric reverse insertion, which was confirmed by FISH. The karyotype of her husband was normal. Conclusion The duplication of 17q23q25 in the fetus has derived from a paracentric reverse insertion of chromosome 17 in its mother. OGM has the advantage for delineating balanced chromosome structural abnormalities.

    染色体畸变17号染色体光学基因组图谱荧光原位杂交单核苷酸多态性微阵列胎儿

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    6q26q27微重复合并15q26.3微缺失一个家系的遗传学分析

    王丹卢朝升石佳旻陈源...
    733-736页
    查看更多>>摘要：目的 对1个6q26q27微重复合并15q26.3微缺失的家系进行遗传学分析。 方法 选取2021年1月在温州医科大学附属第一医院就诊的1例6q26q27微重复合并15q26.3微缺失的胎儿及其家系成员为研究对象。收集胎儿的临床资料，对胎儿及其父母进行G显带染色体核型分析和染色体微阵列分析(CMA)，对其外祖父母进行核型分析。 结果 产前超声提示胎儿宫内生长发育迟缓。胎儿及其家系成员的核型分析均未见异常。CMA检测提示胎儿携带染色体6q26q27区6.6 Mb的片段重复以及15q26.3区1.9 Mb的片段缺失，其母亲携带相同区域6.49 Mb的重复和1.867 Mb的缺失，其父亲未见异常。 结论 染色体6q26q27微重复和15q26.3微缺失可能是本例胎儿生长发育迟缓的遗传学病因。 Objective To explore the genetic basis for a Chinese pedigree with 6q26q27 microduplication and 15q26.3 microdeletion. Methods A fetus with a 6q26q27 microduplication and a 15q26.3 microdeletion diagnosed at the First Affiliated Hospital of Wenzhou Medical University in January 2021 and members of its pedigree were selected as the study subject. Clinical data of the fetus was collected. The fetus and its parents were analyzed by G-banding karyotyping and chromosomal microarray analysis (CMA), and its maternal grandparents were also subjected to G-banding karyotype analysis. Results Prenatal ultrasound had indicated intrauterine growth retardation of the fetus, though no karyotypic abnormality was found with the amniotic fluid sample and blood samples from its pedigree members. CMA revealed that the fetus has carried a 6.6 Mb microduplication in 6q26q27 and a 1.9 Mb microdeletion in 15q26.3, and his mother also carried a 6.49 duplication and a 1.867 deletion in the same region. No anomaly was found with its father. Conclusion The 6q26q27 microduplication and 15q26.3 microdeletion probably underlay the intrauterine growth retardation in this fetus.

    胎儿6q26q27微重复15q26.3微缺失遗传咨询拷贝数变异

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    17q12微缺失综合征胎儿1例的临床表型及遗传学分析

    吕永雪林梅芳邵洁梁程红...
    737-743页
    查看更多>>摘要：目的 探讨1例17q12微缺失综合征胎儿的临床表型和遗传学特征。 方法 选取2020年6月在湖州市妇幼保健院确诊的1例17q12微缺失综合征胎儿作为研究对象。收集胎儿的临床资料，对孕妇进行羊水穿刺，对胎儿进行染色体核型分析和染色体微阵列分析(CMA)，采集孕妇夫妇的外周血样进行CMA检测，追溯胎儿异常染色体的亲代来源，追踪患儿出生后的临床表型。 结果 产前超声提示羊水增多，胎儿肾脏结构异常。胎儿染色体核型为46，XN，CMA结果提示其染色体17q12区存在1.9 Mb的杂合缺失，涉及HNF1B、ACACA、ZNHIT3、CCL3L1、PIGW等5个OMIM基因，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。胎儿父母CMA检测均未见异常。患儿出生后主要表现为肾囊肿和脑结构异常，结合产前基因表型，确诊为17q12微缺失综合征。 结论 17q12微缺失综合征胎儿在出生后的随访中出现了肾脏及脑结构异常改变，可能与HNF1B等基因的功能缺陷密切相关。 Objective To explore the clinical phenotype and genetic characteristics of a fetus with 17q12 microdeletion syndrome. Methods A fetus with 17q12 microdeletion syndrome who was diagnosed at Huzhou Maternal & Child Health Care Hospital in June 2020 was selected as the study subject. Clinical data of the fetus was collected. The fetus was subjected to chromosomal karyotyping and chromosomal microarray analysis (CMA). To determine the origin of fetal chromosomal abnormality, its parents were also subjected to CMA assay. The postnatal phenotype of the fetus was also investigated. Results Prenatal ultrasound revealed polyhydramnios and fetal renal dysplasia. The fetus was found to have a normal chromosomal karyotype. CMA has detected a 1.9 Mb deletion in the 17q12 region, which has encompassed five OMIM genes including HNF1B, ACACA, ZNHIT3, CCL3L1 and PIGW. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the 17q12 microdeletion was predicted as pathogenic copy number variation (CNV). CMA analysis has detected no pathogenic CNV in both parents. After birth, the child was found to have renal cysts and abnormal brain structure. Combined with the prenatal findings, the child was diagnosed with 17q12 microdeletion syndrome. Conclusion The fetus has 17q12 microdeletion syndrome presenting as abnormalities of the kidney and central nervous system, which are strongly correlated with functional defects of the deletion region involving the HNF1B and other pathogenic genes.

    产前诊断17q12微缺失综合征肾囊肿胎儿

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    46，X，ins(X；12)伴胚胎停育1例

    李晓丽张晓妮蓝信强梁程红...
    743页
    查看更多>>摘要：女，27岁，于2018年9月12日在我院就诊。系G2P0，第1次怀孕60+ d发生胚胎停育，手术流产；第2次怀孕40+ d发生阴道流血，超声未见胎芽、胎心，手术流产。体格检查：外观、智力及第二性征发育均正常，身高为166 cm，体质量为60 kg。月经结束后5 d内分泌检查结果：卵泡刺激素5.18 U/L，黄体生成素4.12 U/L，雌二醇167.9 pmol/L，孕酮2.15 nmol/L，睾酮0.62 nmol/L，垂体泌乳素0.65 nmol/L，均未见异常。泌尿系统超声未见异常。否认有毒有害物质及放射线接触史。患者母亲月经不规律，曾有1次自然流产史，无兄弟姐妹。丈夫年龄为28岁，身体健康，否认家族遗传病史，夫妇双方否认近亲结婚。为进一步明确流产的原因，对其第2次流产组织及夫妻双方的外周血样进行染色体核型分析。本研究通过了我院伦理委员会的审查(WHFY-YXLLWYH-L2022013)，夫妇双方均签署了知情同意书。
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    Y长臂部分缺失伴X单体嵌合性发育异常胎儿1例的产前诊断及遗传学分析

    王丽娟郭辉林琪胡芷洋...
    744-749页
    查看更多>>摘要：目的 对1例性发育异常(DSDs)胎儿进行产前诊断和遗传学分析。 方法 选取2021年9月于深圳市人民医院发现的1例DSDs胎儿为研究对象。联合应用荧光定量PCR(QF-PCR)、多重连接探针扩增(MLPA)、染色体微阵列分析(CMA)、实时荧光定量PCR(qPCR)等分子遗传学技术以及核型分析、荧光原位杂交(FISH)等细胞遗传学技术进行分析。用超声检查胎儿性发育的情况。 结果 分子遗传学检测提示胎儿可能存在Yq11.222qter缺失与X单体的嵌合，结合细胞遗传检测确定其核型为mos 45，X[34]/46，X，del(Y)(q11.222)[61]/47，X，del(Y)(q11.222)，del(Y)(q11.222)[5]，超声检查发现胎儿存在尿道下裂，产前诊断胎儿为DSDs，引产后证实。 结论 综合应用多种遗传学检测技术及超声检查，完成了1例具有复杂核型的DSDs胎儿的产前诊断。 Objective To carry out prenatal diagnosis and genetic analysis for a fetus with disorders of sex development (DSDs). Methods A fetus with DSDs who was identified at the Shenzhen People's Hospital in September 2021 was selected as the study subject. Combined molecular genetic techniques including quantitative fluorescence PCR (QF-PCR), multiplex ligation-dependent probe amplification (MLPA), chromosomal microarray analysis (CMA), quantitative real-time PCR (qPCR), as well as cytogenetic techniques such as karyotyping analysis and fluorescencein situ hybridization (FISH) were applied. Ultrasonography was used to observe the phenotype of sex development. Results Molecular genetic testing suggested that the fetus had mosaicism of Yq11.222qter deletion and X monosomy. Combined with the result of cytogenetic testing, its karyotype was determined as mos 45, X[34]/46, X, del(Y)(q11.222)[61]/47, X, del(Y)(q11.222), del(Y)(q11.222)[5]. Ultrasound examination suggested hypospadia, which was confirmed after elective abortion. Combined the results of genetic testing and phenotypic analysis, the fetus was ultimately diagnosed with DSDs. Conclusion This study has applied a variety of genetic techniques and ultrasonography to diagnose a fetus with DSDs with a complex karyotype.

    性分化障碍嵌合体产前诊断Y染色体长臂部分缺失胎儿

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