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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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    Al Kaissi综合征1例患儿的基因变异分析及文献复习

    孙阁阁赵干业胡爽任化楠...
    193-198页
    查看更多>>摘要：目的 探讨1例Al Kaissi综合征患儿的遗传学病因，并为其家系提供产前诊断。 方法 选取2021年3月6日于河南省郑州大学第一附属医院就诊的1例Al Kaissi综合征患儿为研究对象。提取患儿基因组DNA，应用拷贝数变异测序(CNV-seq)和全外显子组测序(WES)技术对患儿进行遗传变异筛查，应用PCR-琼脂糖凝胶电泳和实时荧光定量PCR技术(qPCR)对筛查结果进行验证，同时验证其父母以明确变异来源，并对该家系的产前绒毛样本进行检测。 结果 患儿为6岁4个月男性，具有低耳位、招风耳和三角脸等特殊面容，语言和智力发育迟缓，存在先天性室间隔缺损。CNV-seq结果未见明显异常，WES结果提示患儿CDK10基因第1、2外显子纯合缺失，PCR-琼脂糖凝胶电泳和qPCR结果进一步证实患儿父母均为CDK10基因第1、2外显子杂合缺失携带者。该家系产前绒毛样本提示胎儿为CDK10基因第1、2外显子杂合缺失携带者。 结论 结合临床表型，上述患儿考虑为CDK10基因第1、2外显子纯合缺失所致的Al Kaissi综合征。 Objective To explore the genetic etiology of a child with delayed growth and development and carry out a literature review. Methods A child suspected for Al Kaissi syndrome at the First Affiliated Hospital of Zhengzhou University on March 6, 2021 was selected as the study subject. Following extraction of genomic DNA, the child was subjected to copy number variation sequencing (CNV-seq) and whole exome sequencing (WES), and candidate variants were verified by PCR-agarose gel electrophoresis and quantitative real-time PCR (qPCR). Prenatal diagnosis was conducted on chorionic villi sample upon subsequent pregnancy. Results The child, a 6-year-and-4-month-old boy, has dysmorphic features including low-set protruding ears and triangular face, delayed language and intellectual development, and ventricular septal defect. CNV-seq result has found no obvious abnormality, whilst WES revealed homozygous deletion of exons 1 and 2 of the CDK10 gene, which was confirmed by PCR -agarose gel electrophoresis and qPCR. Both of his parents were heterozygous carriers. Prenatal diagnosis using chorionic villi samples suggested that the fetus also carried the heterozygous deletion. Conclusion The clinical features of Al Kaissi syndrome in this child can probably be attributed to the homozygous deletion of exons 1 and 2 of the CDK10 gene.

    全外显子组测序CDK10基因AlKaissi综合征产前诊断

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    3-羟基-3-甲基戊二酰辅酶A裂解酶缺乏症2例患儿的临床及遗传学分析

    吴雪付东霞王会贞毋盛楠...
    199-204页
    查看更多>>摘要：目的 探讨3-羟基-3-甲基戊二酰辅酶A裂解酶缺乏症(HMGCLD)患儿的临床特征和基因变异。 方法 选择分别于2019年12月和2022年6月在河南省儿童医院确诊的2例HMGCLD患儿作为研究对象。收集患儿的临床资料、实验室检查以及基因检测结果，分析其临床和遗传学特点。 结果 患儿均表现为反复抽搐、严重低血糖、代谢性酸中毒、肝功能异常等，血氨基酸及酰基肉碱谱中3-羟基-异戊酰肉碱(C5OH)、3-羟基-异戊酰肉碱/辛酰肉碱比值(C5OH/C8)升高，尿有机酸分析3-羟基-3-甲基戊二酸、3-甲基戊二酸、3-甲基戊烯二酸、3-羟基异戊酸及3-甲基巴豆酰甘氨酸增多。患儿1携带HMGCL基因c.722C>T纯合变异，评级为临床意义未明变异(PM2_Supporting＋PP3)。患儿2携带HMGCL基因c.121C>T纯合变异，评级为致病性变异(PVS1＋PM2_Supporting＋PP4)。 结论 HMGCLD的急性发作期多表现为低血糖、代谢性酸中毒等代谢紊乱，尿中升高的有机酸有助于鉴别诊断，但确诊有赖于基因检测。 Objective To explore the clinical characteristics and genetic variants of two children with 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMGCLD). Methods Two children with HMGCLD diagnosed at Henan Provincial Children′s Hospital respectively in December 2019 and June 2022 were selected as the study subjects. Clinical data and results of laboratory testing were analyzed retrospectively. Results Both children had manifested with repeated convulsions, severe hypoglycemia, metabolic acidosis and liver dysfunction. Blood amino acids and acylcarnitine analysis showed increased 3-hydroxy-isovalyl carnitine (C5OH) and 3-hydroxy-isovalyl carnitine/capryloyl carnitine ratio (C5OH/C8), and urinary organic acid analysis showed increased 3-hydroxyl-3-methyl glutaric acid, 3-methyl glutaric acid, 3-methyl glutacoic acid, 3-hydroxyisoglycine and 3-methylprotarylglycine. Child 1 was found to harbor homozygous c. 722C>T variants of theHMGCL gene, which was rated as uncertain significance(PM2_Supporting+ PP3). Child 2 was found to harbor homozygous c. 121C>T variants of theHMGCL gene, which was rated as pathogenic(PVS1+ PM2_Supporting+ PP4). Conclusion Acute episode of HMGCLD is usually characterized by metabolic disorders such as hypoglycemia and metabolic acidosis, and elevated organic acids in urine may can facilitate the differential diagnosis, though definite diagnosis will rely on genetic testing.

    3-羟基-3-甲基戊二酰辅酶A裂解酶缺乏症低血糖代谢性酸中毒HMGCL基因

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    SHOX基因杂合性缺失2例胎儿的产前诊断及表型分析

    顾雷雷刘威朱湘玉李洁...
    205-208页
    查看更多>>摘要：目的 探讨2例SHOX基因杂合缺失胎儿的临床表型及产前诊断。 方法 选择2022年6月24日和2022年7月27日就诊于南京大学医学院附属鼓楼医院的2名孕妇及其发育迟缓胎儿作为研究对象。采集胎儿的羊水样品，提取基因组DNA，进行单核苷酸多态性微阵列(SNP array)检测和/或FGFR3基因变异检测。 结果 排除FGFR3基因变异影响后，胎儿1的Xp或Yp末端存在约883 kb的杂合性缺失，胎儿2的Xp末端存在约5.75 Mb的杂合性缺失，2个缺失片段均包含SHOX基因。其中胎儿1的缺失片段来源未知，胎儿2的缺失片段遗传自母亲。胎儿1足月娩出，外观未见异常；胎儿2尚在妊娠中。 结论 结合超声提示异常、亲代表型及SNP array结果，可解释胎儿的宫内发育迟缓的表型及预测出生后的表型，有助于产前诊断。 Objective To explore the clinical manifestations of two fetuses harboring heterozygous deletions of the SHOX gene. Methods Two pregnant women who had presented at the Prenatal Diagnosis Center of Nanjing Drum Tower Hospital respectively on June 24, 2022 and July 27, 2022 were selected as the study subjects. In case 1, prenatal ultrasonography had shown short femur and intrauterine growth retardation of the fetus. Case 2 had a history of spontaneous abortions due to structural chromosomal aberrations. Fetus 1 had undergone a test for the FGFR3 gene, and both fetuses were subjected to single nucleotide polymorphism-based microarray (SNP array) analysis. Results Affter excluding the influence of FGFR3 gene Fetus 1 was found to harbor a heterozygous 883 kb deletion at Xpter or Ypter, whilst fetus 2 was found to harbor a 5.75 Mb deletion in the Xpter region. Both deletions have encompassed the SHOX gene. The origin of the deletion in fetus 1 was unknown, whilst that in fetus 2 was inherited from its mother. Fetus 1 has been delivered at term with a normal phenotype, and fetus 2 was not born yet. Conclusion The intrauterine and postnatal phenotypes of fetuses may be predicted by combining the ultrasound finding, parental phenotype and results of CMA, variant, and the results can facilitate genetic counseling and decision making over the pregnancy.

    染色体微阵列分析产前诊断SHOX基因

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    SBDS基因变异致Shwachman-Diamond综合征1例患儿的临床及遗传学分析

    李素丽于志丹周方王欢...
    209-214页
    查看更多>>摘要：目的 探讨1例SBDS基因变异致Shwachman-Diamond综合征(SDS)患儿的临床特点及基因变异情况。 方法 选择2022年2月因"间断腹泻、便血7月余"就诊于郑州大学附属儿童医院消化科1例SDS女性患儿作为研究对象，收集其临床资料。收集患儿、患儿父母及其姐姐的外周血样，进行全外显子组测序，并进行Sanger测序验证。 结果 患儿为1岁1月龄女性，主要表现为腹泻、便血、生长发育迟缓、营养不良，血液转氨酶升高，中性粒细胞和血红蛋白降低。左手腕部正位X射线摄片显示骨龄明显落后。肠镜检查发现结直肠黏膜糜烂，肠腔内可见较多油性食物残渣附着。基因测序显示患儿SBDS基因存在父源c.258＋2T>C和母源c.100A>G复合杂合变异。c.258＋2T>C为已报道致病性变异。根据美国医学遗传学与基因组学学会变异评级指南，c.100A>G变异评级为可能致病性变异(PM1＋PM2_Supporting ＋PM3＋PM5＋ PP3)。 结论 c.258＋2T>C和c.100A>G复合杂合变异考虑是该SDS患儿致病原因。对于难治性腹泻、肝损害和生长迟缓的患儿，需警惕SDS，基因检测有利于明确诊断及指导治疗。 Objective To analyze the clinical features and genetic characteristics of a patient with Shwachman-Diamond syndrome (SDS) due to compound heterozygous variants of SBDS gene. Methods A female child with SDS who was admitted to the Children's Hospital Affiliated to Zhengzhou University in February 2022 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and her elder sister and parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. Results The child, a 1-year-and-1-month-old girl, had mainly manifested with diarrhea, hematochezia, growth retardation and malnutrition, along with increased transaminases and decreased neutrophils and hemoglobin. The anteroposterior X-ray of her left wrist indicated significantly delayed bone age. Colonoscopy revealed that her colorectal mucosa was erosive with oily food residues attached to the intestinal lumen. Genetic testing revealed that she has harbored c. 258+ 2T>C and c. 100A>G compound heterozygous variants of theSBDS gene. The c. 258+ 2T>C variant has derived from her father and known to be pathogenic, whilst the other has derived from her mother. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 100A>G variant was classified as likely pathogenic (PM1+ PM2_Supporting+ PM3+ PM5+ PP3). Conclusion The compound heterozygous variants of c. 258+ 2T>C and c. 100A>G probably underlay the SDS in this child. For children with refractory diarrhea, liver damage and growth retardation, SDS should be suspected, and genetic testing can facilitate the diagnosis and treatment.

    SBDS基因Shwachman-Diamond综合征基因变异儿童

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    成年起病的球形细胞脑白质营养不良1例患者的遗传学分析

    梁文文朱舟方永康鞠翠钰...
    215-220页
    查看更多>>摘要：目的 探讨1例成年型球形细胞脑白质营养不良/Krabbe病(KD)患者的临床特征与遗传学病因。 方法 选取2022年2月15日因"右下肢无力进行性加重4年余"于华中科技大学同济医学院附属同济医院神经内科就诊的1例KD患者为研究对象。对患者进行临床、影像学及基因变异分析并进行家系验证。 结果 患者为36岁女性，以痉挛性步态为主要临床表现。头颅MRI示双侧皮质脊髓束走行区对称性病变，白细胞β-半乳糖脑苷脂酶(GALC)活性明显降低。患者的GALC基因存在c.461C>A(p.Pro154His)及c.1901T>C(p.Leu634Ser)复合杂合错义变异，其母亲、姐姐及外甥均携带c.461C>A(p.Pro154His)杂合变异，其父亲携带c.1901T>C(p.Leu634Ser)杂合变异。 结论 患者最终被诊断为成年型KD。GALC基因c.461C>A(p.Pro154His)及c.1901T>C(p.Leu634Ser)复合杂合变异可能是其遗传学病因。 Objective To explore the clinical features and genetic etiology of a patient with adult-onset globoid cell leukodystrophy/Krabbe disease (KD). Methods A patient who was admitted to the Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology on February 15, 2022 due to exacerbation of right leg weakness for over 4 years was selected as the study subject. Clinical data and results of medical imaging and genetic analysis were analyzed. Candidate variants were verified by family analysis. Results The patient, a 36-year-old woman, had spasmodic gait as the primary presentation. Cranial magnetic resonance imaging (MRI) revealed symmetrical abnormalities in the bilateral corticospinal tracts, and the activity of β-galactocerebrosidase (GALC) in her white blood cells was significantly decreased. The patient was found to harbor compound heterozygous variants of the GALC gene, namely c.461C>A (p.Pro154His) and c. 1901T>C (p.Leu634Ser). Her mother, sister and nephew were heterozygous carriers of the c. 461C>A (p.Pro154His) variant, whilst her father was heterozygous for the c.1901T>C (p.Leu634Ser) variant. Conclusion The patient was ultimately diagnosed with adult-onset KD, for which the compound heterozygous variants of the GALC gene may be accountable.

    Krabbe病半乳糖脑苷脂酶对称性皮质脊髓束病变复合杂合变异

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    TMEM67基因变异所致Meckel综合征1例胎儿的遗传学分析

    唐慧宋小艳翁欣刘敏娟...
    221-224页
    查看更多>>摘要：目的 对1例Meckel综合征(MKS)胎儿进行产前诊断，明确其致病原因。 方法 选取2018年2月就诊于苏州市立医院的1例孕妇作为研究对象，收集其临床信息。采集引产胎儿肌肉组织标本以及孕妇夫妇的外周血样，进行染色体微阵列分析(CMA)和全外显子组测序，并用Sanger测序对候选变异进行验证。 结果 孕18周超声提示胎儿存在小头畸形、小脑香蕉征、多囊肾和羊水过少。引产后观察到胎儿脑膨出、多指和肾脏囊形结构。胎儿CMA检测未见异常。基因测序提示引产胎儿TMEM67基因存在母源c.296delA(p.Lys99SerfsTer6)和父源c.1243G>A(p.Val415Met)变异。根据美国医学遗传学与基因组学学会变异相关指南，c.296del被评级为致病性变异(PVS1＋PM2_Supporting＋PP4)，c.1243G>A被评级为可能致病性变异(PM2_Supporting＋PM3＋PP3_Moderate＋PP4)。 结论 TMEM67基因c.296delA和c.1243G>A变异可能是该MKS胎儿的遗传学病因。 Objective To carry out prenatal diagnosis for a fetus with Meckel syndrome(MKS) and explore its genetic basis. Methods A pregnant woman presented at Suzhou Municipal Hospital in February 2018 was selected as the study subject. Clinical data was collected. Muscle tissue sample from the abortus and peripheral blood samples from the couple were collected. Genomic DNA was extracted and subjected to chromosomal microarray analysis (CMA) and whole exome sequencing. Candidate variant was verified by Sanger sequencing. Results The fetus was found to have microcephaly, oligohydramnios, polycystic kidneys and banana-shaped cerebellum at 18 weeks of gestation. After induction of labor, it was found to have encephalocele, renal cysts and polydactyly. CMA has found no abnormality. Whole exome sequencing revealed novel compound heterozygous variants c. 296delA (p.Lys99SerfsTer6) and c. 1243G>A (p.Val415Met) in theTMEM67 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 296delA variant was predicted to be pathogenic (PVS1+ PM2_Supporting+ PP4), whilst the c. 1243G>A variant was predicted to be likely pathogenic (PM2_Supporting+ PM3+ PP3_Moderate+ PP4). Conclusion The c. 296delA and c. 1243G>A compound heterozygous variants of theTMEM67 gene probably underlay the MKS in this fetus.

    Meckel综合征TMEM67基因全外显子组测序

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    ASPA基因变异所致Canavan病1例患儿的临床及遗传学分析

    牛莎莎马燕燕律玉强辛红美...
    225-229页
    查看更多>>摘要：目的 对1例Canavan病(CD)患儿进行临床表型及遗传学分析。 方法 选取1例因"发现竖头不稳2个月，四肢肌张力高1周"于2021年4月9日就诊于山东大学附属儿童医院的患儿进行高通量全外显子组测序检测，并对候选变异进行Sanger测序家系验证。 结果 测序结果显示患儿ASPA基因存在父源c.556_559dupGTTC(p.L187Rfs*5)和母源c.919delA(p.S307Vfs*24)复合杂合变异。根据美国医学遗传学与基因组学学会变异相关指南，二者均被评级为致病性变异(PVS1＋PM2_Supporting＋PM3)。 结论 ASPA基因c.556_559dupGTTC(p.L187Rfs*5)和c.919delA(p.S307Vfs*24)复合杂合变异可能是该CD患儿的致病原因。 Objective To analyze the clinical phenotype and genetic characteristics for a child with Canavan disease. Methods A child who was admitted to the Children's Hospital Affiliated to Shandong University on April 9, 2021 for inability to uphold his head for 2 months and increased muscle tone for one week was subjected to whole exome sequencing, and candidate variants were verified by Sanger sequencing. Results Genetic testing revealed that the child has harbored compound heterozygous variants of the ASPA gene, including a paternally derived c. 556_559dupGTTC (p. L187Rfs*5) and a maternally derived c.919delA (p. S307Vfs*24). Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+ PM2_Supporting+ PM3). Conclusion The c. 556_559dupGTTC (p.L187Rfs*5) and c. 919delA (p.S307Vfs*24) compound heterozygous variants of the ASPA gene probably underlay the pathogenesis of Canavan disease in this child.

    Canavan病ASPA基因高通量测序Sanger测序儿童

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    Cowden综合征1型1例患儿的临床表型与遗传学分析

    闫露露田丽蕴张玉鑫刘颖文...
    230-233页
    查看更多>>摘要：目的 探讨1例Cowden综合征1型(CS1)患儿的遗传学原因，明确其致病原因。 方法 选取2022年8月26日在宁波市妇女儿童医院就诊的1例CS1患儿作为研究对象，收集患儿的临床资料。采集外周血样提取DNA，进行全外显子组测序(WES)，并通过Sanger测序技术对候选变异进行验证。 结果 患儿为13岁男性，表现为智力严重低下，精神异常亢奋、自闭症行为，牙齿稀疏且突出，巨头畸形和阴茎头色素性斑点斑。患儿母亲主要表现为多发处乳头状丘疹，错构瘤形息肉，甲状腺腺瘤和巨头畸形。WES检测结果提示患儿携带PTEN基因c.781C>T( p．Q261*)杂合变异，遗传自母亲。依据美国医学遗传学和基因组学学会指南，c.781C>T变异评判为可能致病性变异(PVS1＋PM2_Supporting)。 结论 PTEN基因c.781C>T变异考虑为该CS1患儿及其母亲的致病原因，上述发现有助于对该家系进行遗传咨询。 Objective To explore the genetic etiology of a child with Cowden syndrome 1 (CS1). Methods A child who had visited the Ningbo Women and Children's Hospital on August 26, 2022 was selected as the study subject. Clinical information of the child was collected. Genomic DNA was extracted from peripheral blood samples of the child and his family members and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. Results The child, a 13-year-old boy, had manifested with severe mental retardation, hyperactivity, autistic behavior, sparse and prominent teeth, macrocephaly, and skin freckles on the penis. His mother had presented with multiple papules, hamartomatous polyps, thyroid adenoma and macrocephaly. WES results revealed that the child has harbored a nonsense c. 781C>T (p.Q261*) variant of thePTEN gene, which was inherited from his mother. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.781C>T variant was classified as likely pathogenic (PVS1+ PM2_Supporting). Conclusion The c. 781C>T variant of thePTEN gene probably underlay the pathogenesis in the child and his mother. Above finding has facilitated genetic counseling for this family.

    Cowden综合征1型PTEN基因无义变异全外显子组测序儿童

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    MORC2基因新发变异导致DIGFAN综合征1例的遗传学分析

    谢波波范歆魏贤达桂宝恒...
    234-238页
    查看更多>>摘要：目的 探讨1例发育迟缓、生长落后、面部畸形和轴突神经病变(DIGFAN)患儿的临床表现和遗传学病因。 方法 选取2021年3月22日因"身材矮小、智力发育落后"就诊于广西医科大学第二附属医院儿童内分泌遗传代谢门诊的1例患儿作为研究对象，收集其临床资料。采集患儿及其父母的外周血样，进行全外显子组测序，确定候选变异，并对其家系进行Sanger测序验证。利用生物信息软件对变异位点进行致病性评估及蛋白模拟分析。 结果 患儿为10岁9月龄男性，存在身材矮小、智力发育落后、语言和运动发育迟缓、面部畸形等临床特征。基因测序提示患儿MORC2基因存在c.800T>C(p.Leu267Pro)杂合变异，Sanger测序验证为新发变异。该变异所在的氨基酸Leu267在不同物种间高度保守。Leu267位于MORC2蛋白的ATP酶结合区的核糖体蛋白S5结构域，Leu267Pro可能通过影响ATP酶的空间构象和活性，从而影响MORC2蛋白的功能。根据美国医学遗传学与基因组学学会基因变异评级相关指南，c.800T>C评级为可能致病性变异(PS2＋PM2_Supporting＋PP2＋PP3)。 结论 MORC2基因c.800T>C(p.Leu267Pro)变异考虑为该DIGFAN患儿的遗传学病因。 Objective To explore the clinical features and genetic etiology for a child with developmental delay, impaired growth, facial dysmorphism, and axonal neuropathy (DIGFAN). Methods A child who was admitted to the Second Affiliated Hospital of Guangxi Medical University on March 22, 2021 was selected the study subject. Clinical data of the child was collected. Following extraction of genomic DNA, the child and his parents were subjected to whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing and bioinformatic analysis. Results The child, a 10-year-and-9-month-old boy, had manifested with short stature, intellectual disability, delayed speech, motor and language development, and facial dysmorphism. WES and Sanger sequencing revealed that he has harbored a novel de novo c. 800T>C (p.Leu267Pro) variant of theMORC2 gene. The Leucine at position 267, which is highly conserved among various species, is located in the S5 domain of ribosome protein in the ATPase binding region of MORC2. And the Leu267Pro may affect the function of MORC2 by altering the spatial conformation and activity of ATPase. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 800T>C variant was classified as likely pathogenic (PS2+ PM2_Supporting+ PP2+ PP3). Conclusion The MORC2: c. 800T>C (p.Leu267Pro) variant probably underlay the pathogenesis of DIGFAN syndrome in this child.

    神经系统疾病发育迟缓生长落后面部畸形轴突神经病变MORC2基因新发变异儿童

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    NR5A1基因变异致46, XY性发育异常1例患者的遗传学分析

    刘爱玲武明莉李萍彭海英...
    239-243页
    查看更多>>摘要：目的 分析1例性发育异常(DSD)患儿的临床特征，探讨其遗传学病因。 方法 选取2019年7月29日因原发闭经就诊于临沂市人民医院遗传咨询门诊的1例DSD患儿作为研究对象，收集其临床资料。应用染色体核型分析及实时荧光定量PCR检测Y染色体微缺失，分析患儿染色体是否存在异常。利用高通量测序对患儿及父母进行基因检测，对候选变异进行Sanger测序验证，对变异位点进行致病性评估。 结果 患儿年龄为13岁，社会性别女，存在原发性闭经，男性第二性征发育，超声检查未探及子宫及明确卵巢结构，可探及窄带样阴道低回声及弯曲阴茎海绵体样结构。患儿染色体核型为46, XY，Y染色体AZF区段不存在缺失。基因测序发现患儿存在母源的NR5A1：c.323delA(p.Q108Rfs*188)。根据美国医学遗传学与基因组学学会(ACMG)遗传变异分类标准与指南，NR5A1：c.323delA变异评级为致病性变异(PVS1＋PM2_Supporting＋PP4)。 结论 NR5A1：c.323delA变异考虑是该DSD患儿的致病原因，为临床诊断和治疗提供遗传学依据。 Objective To analyze the clinical features and genetic basis of a child with Disorder of sex development (DSD). Methods A child who was admitted to the Linyi People′s Hospital for primary amenorrhoea on July 29, 2019 was selected as the study subject. Clinical data of the child was collected. Chromosomal karyotyping and quantitative real-time PCR were used to detect Y chromosome microdeletions and other chromosomal aberrations. Next-generation sequencing was carried out for the child and her parents. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. Results The child, a 13-year-old girl, has featured primary amenorrhoea and onset of secondary sex characteristics of males. Ultrasound exam had detected no uterus and definite ovarian structure, but narrow band vaginal hypoecho and curved cavernoid structure. The child was found to have a 46, XY karyotype without an AZF deletion. DNA sequencing revealed that she has harbored a maternally derived c. 323delA (p.Q108Rfs*188) variant in the nuclear receptor subfamily 5 group A member 1 (NR5A1) gene, which may result in a truncated protein. The variant was classified as pathogenic (PVS1+ PM2_Supporting+ PP4) based on the guidelines from the American College of Medical Genetics and Genomics. Conclusion The NR5A1: c. 323delA variant probably underlay the pathogenesis of 46, XY DSD in this child. The discovery of the novel variant has enriched the mutational spectrum of NR5A1 gene and provided a basis for clinical diagnosis, treatment and prenatal diagnosis.

    性发育性染色体障碍NR5A1基因实时荧光定量聚合酶链反应儿童

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