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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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    Schuurs-Hoeijmakers综合征产前诊断1例

    苏利沙朱晓帆吴庆华孔祥东...
    1373-1376页
    查看更多>>摘要：目的 探讨1例Schuurs-Hoeijmakers综合征(SHS)胎儿的遗传学病因，为其产前诊断提供依据。 方法 选取2021年3月20日因胎儿超声异常到郑州大学第一附属医院门诊进行咨询的1名孕妇及其胎儿作为研究对象，收集胎儿临床资料和超声检查结果。羊膜腔穿刺获得胎儿羊水细胞进行常规G显带染色体核型分析及低深度全基因组拷贝数变异(CNV)检测(CNV-seq)，全外显子组测序(WES)筛查胎儿可疑致病基因变异，Sanger测序进行家系验证。 结果 胎儿在胎龄21+5周超声提示颈后皱褶增厚(9.0 mm)，双肾实质回声增强，腹腔积液，左侧胸腔积液，右移心。孕妇既往1次妊娠胎儿多发畸形。胎儿羊水细胞染色体核型分析和CNV-seq检测结果均未见异常。WES提示胎儿携带PACS1基因c.607C>T(p.Arg203Trp)杂合变异，Sanger测序验证提示该变异为新发变异。根据ACMG变异评级指南，c.607C>T(p.Arg203Trp)变异评级为疑似致病变异(PS2+PM2_Supporting+PP3)。 结论 PACS1基因c.607C>T(p.Arg203Trp)杂合变异是该SHS胎儿多发异常的遗传学病因。针对多发结构异常胎儿，CNV未发现异常情况下进行全外显子组测序能够提高胎儿遗传学病因检出率。 Objective To explore the genetic basis for a fetus with multiple malformations. Methods Clinical data of the fetus was collected, Amniotic fluid sample of the fetus was subjected to conventional G-banded karyotyping, low-depth whole genome copy number variants detection and whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing of the fetus and its parents. Results Prenatal ultrasound scan at 21+ 5 gestational weeks had revealed increased nuchal thickness (9.0 mm), enhanced echos of bilateral renal parenchyma, seroperitoneum, left pleural effusion and right displacement of the heart. The mother had a previous history of terminated pregnancy for multiple fetal anomalies. No abnormality was found by conventional karyotyping and CNV analysis, though WES revealed that the fetus has harbored a de novo heterozygous c. 607C>T (p.Arg203Trp) variant of theACS1 gene (NM_018026.3), and the result was validated by Sanger sequencing. Conclusion Through WES and prenatal ultrasonography, the fetus was diagnosed with Schuurs-Hoeijmakers syndrome due to the heterozygous c. 607C>T (p.Arg203Trp) variant of thePACS1 gene (NM_018026.3). For fetuses with multiple malformations, WES can help to reveal the genetic etiology when CNV result is negative.

    Schuurs-hoeijmakers综合征PACS1基因全外显子测序产前诊断

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    CLPB基因新变异所致3-甲基戊烯二酸尿症Ⅶ型患儿1例的临床特征和遗传学分析

    蔺朋武冯暄郝胜菊惠玲...
    1377-1381页
    查看更多>>摘要：目的 探讨1例3-甲基戊烯二酸尿症Ⅶ型患儿的临床特征及基因变异特点。 方法 以2019年8月9日就诊于甘肃省妇幼保健院的1例患儿作为研究对象。收集患儿家系的临床资料，包括尿气相色谱质谱检测结果，应用全外显子组测序技术对患儿及其父母进行分析。 结果 患儿为女性，主要表现为出生后间断皮肤青紫，惊厥，低镁血症，呼吸暂停，中性粒细胞减少。尿液3-甲基戊烯二酸水平升高至17.53 μmol/L。基因测序结果提示患儿携带CLPB基因存在c.1016delT(p.L339Rfs*5)和c.1087A>G(p.R363G)复合杂合变异，分别遗传自其母亲和父亲，二者既往均未见报道。根据美国医学遗传学和基因组学学会(ACMG)相关指南，分别判定为致病变异和疑似致病变异。 结论 患儿被确诊为3-甲基戊烯二酸尿症Ⅶ型。c.1016delT和c.1087A>G变异的发现丰富了CLPB基因的变异谱。 Objective To explore the clinical features and genetic basis for a child with 3-methylglutaconic aciduria type Ⅶ. Methods A child who was diagnosed at the Gansu Provincial Maternity and Child Health Care Hospital on August 9, 2019 was selected as the study subject. Clinical data of the child, including urine gas chromatography and mass spectrometry, were collected. The child and her parents were subjected to whole exome sequencing. Results The child, a female neonate, had presented mainly with intermittent skin cyanosis, convulsions, hypomagnesemia, apnea, neutropenia after birth. Her urine 3-methylpentenedioic acid has increased to 17.53 μmol/L. DNA sequencing revealed that she has harbored compound heterozygous variants of the CLPB gene, namely c. 1016delT (p.L339Rfs*5) and c. 1087A>G (p.R363G), which were respectively inherited from her mother and father. Both variants were unreported previously. Based on the standards from the American College of Medical Genetics and Genomics (ACMG), the variants were respectively predicted to be pathogenic and likely pathogenic. Conclusion The child was diagnosed with 3-methylglutenedioic aciduria type Ⅶ. Discovery of the c. 1016delT and c. 1087A>G variants has enriched the mutational spectrum of theCLPB gene.

    3-甲基戊烯二酸尿症Ⅶ型CLPB基因全外显子组测序

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    t(3；10；6；18；11)罕见易位一例

    李清鲜李岭
    1381页
    查看更多>>摘要：男，汉族，29岁，外观及智力均无异常，因妻子流产3次接受外周血染色体检查。在征得其知情同意后，抽取夫妻双方外周血样，常规进行淋巴细胞培养，G显带分析，妻子染色体核型未见异常，患者核型为46，XY，t(3；10；6；18；11)(q21；q22；q25；q22；q13)(图1)。
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    ADNP基因热点变异致Helsmoortel-Van der Aa综合征患儿1例的分析及文献回顾

    赵岫苏喆许仲炜苏慧萍...
    1382-1386页
    查看更多>>摘要：目的 总结和分析ADNP基因变异所致Helsmoortel-Van der Aa综合征(HVDAS)患者的表型和生物学特征，为早期诊断该病提供线索。 方法 分析1例由ADNP基因热点变异所致HVDAS患儿的病例资料和基因检测结果，并对相关文献进行回顾。 结果 患儿为2岁女性，以生长落后为主诉，伴有特殊面容、精神运动及语言发育落后、反复呼吸道感染，基因检测发现其携带ADNP基因c.2496_2499delTAAA(p.Asn832Lysfs*81)杂合移码变异，其父母均未携带相同的变异。 结论 尽管HVDAS以智力发育障碍、孤独症谱系障碍和特殊外貌为主要表现，但生长迟缓和乳牙早萌出也是其临床特征。携带ADNP基因热点变异者的表型差异并不明显。 Objective To summarize the clinical features and biological characteristics of Helsmoortel Van der Aa syndrome (HVDAS) due to hotspot mutations of the ADNP gene in order to facilitate early diagnosis. Methods Clinical data and result of genetic testing for a girl with HVDAS due to hotspot mutation of the ADNP gene was summarized. Related literature was also reviewed. Results The patient, a 2-year-old girl, had presented with growth retardation, facial dysmorphism, psychomotor and language delay and recurrent respiratory infections. Whole exome sequencing revealed that she has harbored a heterozygous c. 2496_2499delTAAA (p.Asn832Lysfs*81) variant of the ADNP gene, which was not found in either of her parents. Conclusion Although the typical features of the HVDAS have included intellectual disability and autism spectrum disorders, growth retardation and premature primary tooth eruption may also be present. In addition, the phenotypic difference among individuals carrying hot spot variants of the ADNP gene was not prominent.

    Helsmoortel-VanderAa综合征ADNP基因智力障碍孤独症谱系障碍生长迟缓

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    SMN基因复合杂合变异所致脊髓性肌肉萎缩症1例患儿的家系分析

    古艳李丽萍陈辉徐灵均...
    1387-1391页
    查看更多>>摘要：目的 分析1个脊髓性肌肉萎缩症(SMA)家系SMN1基因的变异情况，为遗传咨询和产前诊断提供依据。 方法 以2020年1月在南昌市第一医院就诊的1个SMA家系作为研究对象。采集其外周血样，提取DNA，用多重连接探针杂交(MLPA)法对患儿及其亲属的SMN基因进行检测，再用二代测序(NGS)对患儿进行变异分析，用Sanger测序法对结果进行验证。同时采集外周血样，提取cDNA，以先证者cDNA为模板甄别点变异在SMN1和SMN2基因中的分布情况。 结果 先证者的SMN1基因存在Exon7+Exon8杂合缺失及c.81G>A复合杂合变异，其中c.81G>A变异遗传自其母亲及外祖，SMN1 Exon7+Exon8杂合缺失遗传自父亲及祖母。其姨妈携带SMN1 c．81G>A杂合缺失，姑姑、姑父及表妹未检测到外显子缺失。通过cDNA扩增和Sanger测序，明确c.81G>A变异位于SMN1基因。 结论 MLPA联合Sanger测序、NGS技术能够明确SMA患者携带的SMN基因的复合杂合变异。 Objective To analyze variants of SMN gene in a Chinese pedigree affected with Spinal muscular atrophy (SMA). Methods A Chinese pedigree diagnosed at the Nanchang First Hospital in January 2020 was selected as the study subject. Peripheral blood samples were collected for the extraction of DNA. All exons of the SMN gene were detected by multiple ligation-dependent probe amplification (MLPA). Potential variants of the SMN gene were also detected by Whole exome sequencing (WES), and the result was verified by Sanger sequencing. cDNA extracted from fresh blood sample was used as a template to verify the location of variant on the SMN genes. Results The proband was found to harbor a heterozygous deletion of the SMN1 Exon7+ Exon8, and a heterozygous c. 81G>A variant. TheSMN1 Exon7+ Exon8 deletion was inherited from her father and grandmother, whilst the c. 81G>A variant was inherited from her mother and maternal grandfather. Her aunt was also a carrier of the heterozygous deletion, while her paternal aunt, her husband, and their daughter were not. cDNA amplification and Sanger sequencing confirmed that the c. 81G>A variant was located in theSMN1 gene. Conclusion MLPA combined with NGS and Sanger sequencing can identify compound heterozygous variants of the SMN gene in the SMA patients.

    脊髓性肌肉萎缩症多重连接探针扩增二代测序基因诊断

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    高通量测序确诊Hermansky-Pudlak综合征5型1例患儿及文献复习

    王东黄静张开慧律玉强...
    1392-1396页
    查看更多>>摘要：目的 探讨Hermansky-Pudlak综合征5型(HPS-5)患者的临床和遗传学特征。 方法 选取2019年10月3日于山东大学附属儿童医院就诊的1例HPS-5患儿为研究对象。收集患儿相关临床资料，应用高通量测序技术对该患儿进行基因变异分析，并进行文献复习。 结果 患儿为1岁5个月女孩，临床表现为自幼眼球震颤，眼底检查发现视网膜大部分色素脱失，易瘀伤。高通量测序结果提示患儿携带HPS5基因复合杂合变异：c.1562_1563delAA(p.F521Sfs*27)和c.1404C>A(p.C468X)，分别遗传自其父亲与母亲。根据美国医学遗传学与基因组学学会(ACMG)相关指南，该两个变异均判定为致病性变异(PVS+PM2_Supporting+PM3+PP4)。已报道的18例HPS-5患者均有眼部问题，大多数有出血倾向；8例携带HPS5基因复合杂合变异，8例携带纯合变异，2例携带双纯合变异，大多数变异为无效变异。 结论 本研究患儿为HPS5基因变异所致HPS-5患者，高通量测序分析为疾病的诊断提供了重要工具。HSP-5患者通常具有典型眼白化病或眼皮肤白化病及出血倾向的临床表现，严重并发症较少，以HPS5基因复合杂合变异和纯合变异为主。 Objective To explore the clinical and genetic characteristics of a patient with Hermansky-Pudlak syndrome type 5 (HPS-5). Methods A child with HPS-5 who had attended the Children′s Hospital Affiliated to Shandong University on October 3, 2019 was selected as the study subject. Clinical data of the child were collected. Genetic variant was analyzed through high-throughput sequencing. A literature review was also carried out. Results The child, a 1-year-and-5-month-old girl, had nystagmus since childhood, lost of retinal pigmentation by fundus examination and easy bruising. High-throughput sequencing revealed that she has harbored compound heterozygous variants of the HPS5 gene, namely c. 1562_1563delAA (p.F521Sfs*27) and c. 1404C>A (p.C468X), which were inherited from his father and mother, respectively. Based on the guidelines from the American College for Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PVS+ PM2_Supporting+ PM3+ PP4). Among 18 previously reported HPS-5 patients, all had had eye problems, and most of them had tendency for bleeding. Eight cases had carried compound heterozygous variants of theHPS5 gene, 8 carried homozygous variants, 2 carried double homozygous variants, and most of them were null mutations. Conclusion The c. 1562_1563delAA (p.F521Sfs*27) and c. 1404C>A (p.C468X) compound heterozygous variants of theHPS5 gene probably underlay the HPS-5 in this child. High-throughput sequencing has provided an important tool for the diagnosis. HSP-5 patients usually have typical ocular albinism and/or oculocutaneous albinism and tendency of bleeding, which are commonly caused by compound heterozygous and homozygous variants of the HPS5 gene, though serious complications have been rare.

    眼白化病Hermansky-Pudlak综合征5型HPS5基因高通量测序

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    SLC6A8基因变异致脑肌酸缺乏综合征1例患儿的临床与遗传学分析

    张赟健丁一峰李奕洁周水珍...
    1397-1403页
    查看更多>>摘要：目的 探讨1例由SLC6A8基因变异所致脑肌酸缺乏综合征(CCDS)患儿的临床表现及遗传学特点。 方法 选取2021年3月5日因"间断抽搐发作1月余"就诊于复旦大学附属儿科医院的1例CCDS患儿作为研究对象，收集其临床资料。应用全外显子组测序(WES)对患儿进行基因变异分析，对可能的变异位点通过Sanger测序进行验证并应用转录组测序(RNA-seq)技术验证剪接变异。 结果 患儿为1岁10月龄男性，精神运动发育落后，1岁9月龄始无热惊厥发作，母亲与外婆均有惊厥发作史，患儿头颅MRS示双侧基底节区及丘脑肌酸峰降低，提示脑肌酸缺乏。WES结果发现患儿X染色体SLC6A8基因存在c.1767+1_1767+2insA剪接变异，母亲及外婆均为该变异杂合子。RNA-seq结果显示患儿SLC6A8基因exon12处存在异常可变剪接事件，该变异导致蛋白发生截短。根据美国医学遗传学与基因组学学会变异指南，c.1767+1_1767+2insA评级为可能致病变异(PVS1_Strong+PM2_Supporting+PP4)。 结论 SLC6A8基因c.1767+1_1767+2insA变异考虑是该CCDS患儿致病原因。该变异的检出丰富了该基因的变异谱。 Objective To explore the clinical features and genetic variant in a child with Cerebral creatine deficiency syndrome (CCDS). Methods A child who had presented at the Affiliated Children′s Hospital of Fudan University on March 5, 2021 was selected as the study subject. Whole exome sequencing (WES) was carried out for the child, and candidate variant was verified by Sanger sequencing. The level of creatine in the brain was determined by magnetic resonance spectroscopy. Results The patient, a 1-year-and-10-month male, had presented with developmental delay and epilepsy. Both his mother and grandmother had a history of convulsions. MRS showed reduced cerebral creatine in bilateral basal ganglia and thalamus. The child was found to harbor a hemizygous splicing variant of the SLC6A8 gene, namely c. 1767+ 1_1767+ 2insA, which may lead to protein truncation. The variant was not found in the public databases. Both his mother and grandmother were heterozygous carriers for the same variant. Conclusion The hemizygous c. 1767+ 1_1767+ 2insA variant of the SLC6A8 gene probably underlay the CCDS in this child. Discovery of the novel variant has also expanded the mutational spectrum of the SLC6A8 gene.

    脑肌酸缺乏综合征发育迟缓癫痫SLC6A8基因

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    IL10RA及 DUOX2复合杂合变异致极早发炎症性肠病1例患儿的遗传学分析

    郑翠芳胡文慧余卓文董岿然...
    1404-1408页
    查看更多>>摘要：目的 探讨1例新生儿期起病的极早发炎症性肠病(VEOIBD)患儿的遗传学病因。 方法 收集1例因"生后6 d以腹泻、发热起病"于2018年5月23日就诊于复旦大学附属儿科医院的VEOIBD患儿的临床及随访资料。对其进行家系全外显子测序(WES)，对可疑致病变异进行Sanger测序及PCR验证。 结果 患儿为4.5岁女性，主要表现为腹泻、发热、生长发育迟缓、直肠阴道瘘、甲状腺功能低下，3.5月龄时因严重的肠粘连及肠梗阻而行肠造瘘术。根据其临床表现、消化内镜、组织病理学检查结果诊断为VEOIBD。该患儿合并先天性甲状腺功能减低症，1月龄起予左旋甲状腺素替代治疗。家系WES发现该患儿DUOX2基因存在c.2654G>T及c.505C>T复合杂合错义变异及IL10RA基因存在c.301C>T杂合错义变异，进一步数据分析发现该患儿IL10RA基因的第1外显子存在333 bp的片段缺失。根据美国医学遗传学与基因组学学会变异评级相关指南(ACMG)，该患儿IL10RA：c.301C>T被评级为致病性变异(PS1+PM3+PP3+PP4)，DUOX2：c.2654G>T变异判定为可能致病性变异(PS3+PM3+PM5)，DUOX2：c.505C>T判定为意义未明变异(PM2_Supporting+PM3+PP4)。 结论 对新生儿期起病的极早发炎症性肠病患儿应尽早行基因检测。合并DUOX2基因变异可能加重了该患儿的临床症状。该结果可为患儿家系的遗传咨询和产前诊断提供帮助，并进一步增加临床医生对该罕见病的认识。 Objective To explore the genetic basis of a child with Very early onset inflammatory bowel disease (VEOIBD). Methods A female child who had presented at the Children′s Hospital of Fudan University on May 23, 2018 due to occurrence of diarrhea and fever 6 days after birth was selected as the study subject. Clinical data of the child was collected. Family-based whole-exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing and PCR of the patient and her parents. Results The child had developed the symptoms 6 days after birth, with main manifestations including diarrhea, fever, failure to thrive, rectovestibular fistula and hypothyroidism. An enterostomy was performed at the age of 3.5 months due to severe intestinal adhesion and obstruction. Based on her clinical manifestations, colonoscopic finding, and results of biopsies, she was diagnosed with VEOIBD in conjunct with congenital hypothyroidism. Replacement treatment of levothyroxine was given since one month of age. Family-based WES revealed that the child has harbored compound heterozygous variants of the DUOX2 gene, namely c. 2654G>T (p.R885L) and c. 505C>T (p.R169W), in addition with a heterozygous c. 301C>T (p.R101W) variant of theIL10RA gene. Re-analysis of the WES data revealed that the patient also had a 333 bp deletion spanning exon 1 of the IL10RA gene (Chr11: 117857034_117857366). Conclusion For patients with VEOIBD, genetic testing is recommended. Presence of additional DUOX2 gene variants might have exacerbated the clinical symptoms in this patient. Above finding has facilitated genetic counseling and prenatal diagnosis for this family, and raised clinicians′ awareness of this rare disease.

    极早发炎症性肠病先天性甲状腺功能减低症DUOX2基因IL10基因IL10R基因

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    合并Graves病与肾上腺皮质腺瘤的Gitelman综合征患者1例的临床及基因变异分析

    乔彦赵景宏曹乐薇李云祥...
    1409-1413页
    查看更多>>摘要：目的 对1例极其罕见Gitelman综合征(GS)合并Graves病与肾上腺皮质腺瘤患者进行临床及基因变异分析。 方法 选取2020年12月21日于南充市中心医院就诊的1例GS合并Graves病与肾上腺皮质腺瘤患者为研究对象。收集该患者相关临床资料，采集患者及其家系成员的外周静脉血样，提取DNA后进行加深全外显子组测序，筛查致病基因。 结果 患者为45岁女性，因发现左侧肾上腺占位就诊，临床检查提示存在Graves病、非促肾上腺皮质激素(ACTH)依赖性Cushing综合征、低钾血症及低镁血症等，MRI提示左侧肾上腺3.8 cm×3.2 cm占位，手术病理证实为肾上腺皮质腺瘤。基因检测提示患者及其妹妹存在SLC12A3基因c.1444-10(IVS11)G>A与c.179(exon1)C>T(p.T60M)的复合杂合变异，分别遗传自其父亲和母亲。根据美国医学遗传学与基因组学学会(ACMG)相关指南，c.1444-10(IVS11)G>A与c.179(exon1)C>T(p.T60M)变异分别评级为意义不明变异(PM2_Supporting+PP3)与可能致病性(PM3_Strong+PM1+PP3)。 结论 GS合并Graves病与肾上腺皮质腺瘤暂未见相关报道，SLC12A3基因c.1444-10(IVS11)G>A变异为新发现的变异，其与c.179(exon1)C>T(p.T60M)组成的复合杂合变异可能为本研究患者的遗传学病因。 Objective To report the clinical and genetic characteristics of a rare case of Gitelman syndrome with comorbid Graves disease and ACTH-independent adrenocortical adenoma. Methods A patient who had presented at the Nanchong Central Hospital on December 21, 2020 was selected as the study subject. Clinical data of the patient was collected. Whole-exome sequencing was carried out on DNA extracted from peripheral venous blood samples from the patient and her family members. Results The patient, a 45-year-old woman, was found to have Graves disease, ACTH-independent Cushing syndrome, hypokalemia and hypomagnesemia following the discovery of an adrenal incidentaloma. MRI scan had revealed a 3.8 cm × 3.2 cm mass in the left adrenal gland. The mass was removed by surgery and confirmed as adrenocortical adenoma. DNA sequencing revealed that the patient and her sister have both harbored compound heterozygous variants of the SLC12A3 gene, namely c. 1444-10(IVS11)G>A and c. 179(exon1)C>T (p.T60M), which were respectively inherited from their father and mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 1444-10(IVS11)G>A and c. 179(exon1)C>T (p.T60M) were respectively classified as a variant of uncertain significance (PM2_Supporting+ PP3) and a likely pathogenic variant (PM3_Strong+ PM1+ PP3). Conclusion The conjunction of Gitelman syndrome with Graves disease and adrenal cortex adenoma is rather rare. The newly discovered c. 1444-10(IVS11)G>A variant of theSLC12A3 gene, together with the heterozygous variant of c. 179(exon1) C>T (p.T60M), probably underlay the pathogenesis in this patient.

    Gitelman综合征肾上腺皮质腺瘤Graves病SLC12A3基因Cushing综合征

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    Y染色体长臂嵌合缺失胎儿1例的遗传学分析

    孟凡荣琚端王秀艳史云芳...
    1414-1419页
    查看更多>>摘要：目的 对1例Y染色体长臂嵌合缺失胎儿提供遗传咨询和产前诊断。 方法 选取2021年7月在天津医科大学总医院就诊的1例无创产前检测(NIPT)提示性染色体高风险的胎儿为研究对象。通过染色体G显带核型分析、荧光原位杂交技术(FISH)、拷贝数变异测序(CNV-seq)、荧光定量PCR(QF-PCR)及超声检查等多种方法联合应用对胎儿进行产前诊断。 结果 胎儿(胎龄23周)羊水细胞染色体核型为45，X，然而FISH检测可见Y染色体信号。脐带血穿刺复核，核型结果为嵌合型染色体异常46，X，+mar[33]/45，X[17]；FISH检测提示69%的细胞可见Y染色体信号；CNV-seq检测结果为seq[19]del(Y)(q11.1q12)(mos) chrY：g.13200001_28820000del(嵌合比例64%)，即包括无精症因子(azoospermia factor，AZF)区域的Y染色体长臂嵌合缺失；应用QF-PCR技术对AZF区域缺失进行验证，与CNV-seq结果一致。最终胎儿核型描述为mos 46，X，del(Y)(q11.1)[33]/45，X[17]。超声检查胎儿未见异常。孕妇终止妊娠，引产儿外观未见异常，外生殖器表现为正常男性。 结论 多种检测技术联合应用有利于准确快速的产前诊断。嵌合性性染色体异常胎儿的出生后表型难以准确评估，应尽可能探索基因型-表型联系，为遗传咨询提供更全面准确的指导。 Objective To carry out prenatal diagnosis for a fetus with mosaicism Yq deletion. Methods A fetus with high risk of sex chromosomes indicated by non-invasive prenatal testing (NIPT) at Tianjin Medical University General Hospital in July 2021 was selected as the study subject. Prenatal diagnosis of the fetus was performed with combined G-banded chromosomal karyotyping, fluorescence in situ hybridization (FISH), copy number variation sequencing (CNV-seq), real-time fluorescence PCR (QF-PCR), and ultrasound examination. Results Analysis of the amniocytes at 23 gestational weeks had yielded a 45, X karyotype. However, FISH had shown signals of Y chromosome. Re-examination by cordocentesis had shown a mosaicism of 46, X, + mar[33]/45, X[17]. FISH showed that 69% of the cells had contained Y chromosome signals.The result of CNV-seq was seq[19]del(Y)(q11.1q12)(mos) chrY: g. 13200001_ 28820000del (mosaicism rate = 64%), which suggested mosaicism for a Yq deletion, which encompassed the azoospermia factor (AZF) region. Deletion of the AZF region was verified by QF-PCR. The fetal karyotype was ultimately determined as mos46, X, del(Y)(q11.1)[33]/45, X[17]. Although ultrasound examination had shown no abnormality in the fetus, the couple had opted to terminate the pregnancy, and the induced fetus had a normal male appearance. Conclusion The combined use of multiple techniques is beneficial for accurate and rapid prenatal diagnosis. For fetuses with mosaicism chromosomal abnormalities, it may be difficult to accurately predict the postnatal phenotype. It is therefore necessary to further explore their genotype-phenotype correlation in order to provide better guidance upon genetic counseling.

    染色体核型分析产前诊断荧光原位杂交拷贝数变异测序无精症因子

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