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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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    光学基因组图谱技术在染色体结构变异检测中的应用

    张志强何姝婧李小兰程宽...
    257-265页
    查看更多>>摘要：目的 探讨光学基因组图谱(OGM)技术在检测环状染色体、平衡易位、插入易位等染色体结构异常中的应用。 方法 收集2022年1月至10月因染色体结构异常在中山大学附属第六医院生殖医学中心接受胚胎植入前遗传学检测并进行OGM和染色体微阵列检测的4例患者的资料进行回顾性分析，同时对部分患者样本采用荧光原位杂交技术进行验证。 结果 1例疑似为平衡易位的患者通过OGM检测出平衡易位，并对断裂点进行了精确定位；2例染色体插入易位的患者中，1例3号染色体插入6号染色体的患者通过OGM检测获得了比核型分析更精细的断裂点位置并确定了染色体片段的插入方向，另1例8号染色体插入Y染色体的患者未能检测到染色体插入的信号；1例环状染色体嵌合体患者未检测到成环信号。 结论 OGM技术准确检测出4例患者是否存在染色体异常，为家系遗传咨询提供依据。 Objective To assess the value of optical genome mapping (OGM) for the detection of chromosomal structural abnormalities including ring chromosomes, balanced translocations, and insertional translocations. Methods Clinical data of four patients who underwent pre-implantation genetic testing concurrently with OGM and chromosomal microarray analysis at the Center of Reproductive Medicine of the Sixth Affiliated Hospital of Sun Yat-sen University from January to October 2022 due to chromosomal structural abnormalities were selected as the study subjects. Some of the results were verified by multi-color fluorescence in situ hybridization. Results The OGM has successfully detected a balanced translocation and fine mapped the breakpoints in a patient. Among two patients with insertional translocations, OGM has provided more refined breakpoint locations than karyotyping analysis in a patient who had chromosome 3 inserted into chromosome 6 and determined the direction of the inserted fragment. However, OGM has failed to detect the chromosomal abnormalit in a patient with chromosome 8 inserted into the Y chromosome. It has also failed to detect circular signals in a patient with ring chromosome mosaicism. Conclusion OGM has successfully detected chromosomal structural variations in the four patients and provided assistance for their diagnosis.

    染色体结构变异光学基因组图谱平衡易位插入易位环状染色体

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    7q11.23重复综合征胎儿9例的产前超声表现及遗传学诊断

    李鹏云郭静车佳崔方英...
    266-270页
    查看更多>>摘要：目的 分析9例7q11.23重复综合征胎儿的产前超声表现及遗传学诊断结果。 方法 收集2017年1月至2021年12月在郑州大学第三附属医院产前诊断中心经染色体微阵列分析(CMA)技术确诊为7q11.23重复综合征的胎儿病例共计9例，回顾性分析其产前超声表现、妊娠结局及随访情况。 结果 9例7q11.23重复综合征胎儿中，5例为侧脑室增宽(其中4例为非孤立性侧脑室增宽，1例为孤立性侧脑室增宽)，1例为室间隔缺损伴三尖瓣轻度反流，1例为心室强光点，另外2例未见异常。5例经家系验证考虑为新发变异，其余4例未进行验证。经遗传咨询，7名受试孕妇选择终止妊娠，2名胎儿足月娩出，随访至今生长发育均未见异常。 结论 该9例7q11.23重复综合征胎儿的产前超声表现多变，CMA技术可为其诊断与遗传咨询提供依据。 Objective To analyze ultrasonographic manifestations and genetic etiology of nine fetuses with 7q11.23 duplication syndrome. Methods Ultrasonographic finding, pregnancy outcome and follow-up of nine fetuses detected at the Prenatal Diagnosis Center of the Third Affiliated Hospital of Zhengzhou University from January 2017 to December 2021 were retrospectively analyzed. Results The fetuses were found to harbor a duplication in the 7q11.23 region by chromosomal microarray analysis (CMA). Among these, five had shown ventriculomegaly, including four syndromic and one non-syndromic. For the remainders, one had ventricular septal defect and mild tricuspid regurgitation, one had echogenic intracardiac focus, whilst another two were normal. Five couples had accepted parental verification, and the results confirmed that the 7q11.23 duplication carried by their fetuses were de novo in origin. Following genetic counseling, seven couples had opted to terminate their pregnancies. Two fetuses were delivered at full term, and follow-up had found no abnormalities. Conclusion Prenatal ultrasonographic manifestations of fetuses with 7q11.23 duplication syndrome are variable. CMA can provide assistance for their diagnosis and genetic counseling.

    产前诊断7q11.23重复综合征产前超声染色体微阵列分析遗传学诊断

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    FBN1基因变异致肢端发育不良6例患者的临床表型及遗传学分析

    于美艳刘小梅冉霓杨召川...
    271-277页
    查看更多>>摘要：目的 分析6例FBN1基因变异所致的肢端发育不良家系的临床表型及遗传学特征。 方法 选取2018年2月至2020年10月就诊于青岛大学附属医院的6例患者作为研究对象，收集患者的临床资料进行回顾性分析。患者进行高通量测序，并用Sanger测序对候选致病变异进行验证。 结果 6例患者均表现为严重的身材矮小(<-3s)、短指，手足短宽。其他的表现还包括关节僵硬、特殊面容、骨龄落后、肝脏肿大、喙状股骨头、腰椎前凸等。基因检测显示6例患者均携带FBN1基因杂合变异：患者1存在第42外显子c.5183C>T(p.A1728V)错义变异，遗传自父亲(患者2)；患者3存在第43外显子c.5284G>A(p.G1762S)错义变异，遗传自母亲(患者4)；患者5存在第42外显子c.5156G>T(p.C1719F)错义变异，考虑为新发变异；患者6存在第43外显子c.5272G>T(p.D1758Y)错义变异，考虑为新发变异。患者1、3、6携带变异均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(ACMG)相关指南，患者5携带的c.5156G>T被评级为致病性变异(PS2＋PM1＋PM2_Supporting ＋PM5＋PP3)。 结论 肢端发育不良6例患者均存在重度矮小，其他的临床表现存在异质性。FBN1基因变异考虑为6例患儿的遗传学病因。 Objective To retrospectively analyze the clinical and genetic characteristics of six patients with Acromicric dysplasia due to variants of the FBN1 gene. Methods Six patients who had visited the Affiliated Hospital of Qingdao University between February 2018 and October 2020 were selected as the study subjects. Clinical data of the patients were collected. High-throughput sequencing was carried out. And candidate variants were verified by Sanger sequencing. Results All of the six patients had presented with severe short stature (< 3s), brachydactyly, short and broad hands and feet. Other manifestations included joint stiffness, facial dysmorphism, delayed bone age, liver enlargement, coracoid femoral head, and lumbar lordosis. Genetic testing revealed that all had harbored heterozygous variants of the FBN1 gene. Patient 1 had harbored a c. 5183C>T (p.A1728V) missense variant in exon 42, which had derived from his father (patient 2). Patient 3 had harbored a c. 5284G>A (p.G1762S) missense variant in exon 43, which had derived from her mother (patient 4). Patient 5 had harbored a c. 5156G>T (p.C1719F) missense variant in exon 42, which wasde novo in origin. Patient 6 had harbored a c. 5272G>T (p.D1758Y) missense variant in exon 43, which was alsode novo in origin. The variants carried by patients 1, 3 and 6 were known to be pathogenic. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the FBN1: c. 5156G>T was rated as a pathogenic variant (PS2+ PM1+ PM2_Supporting + PM5+ PP3). Conclusion All of the six patients had severe short stature and a variety of other clinical manifestations, which may be attributed to the variants of the FBN1 gene.

    肌肉骨骼发育肢端发育不良FBN1基因矮身材

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    苯丙氨酸羟化酶基因c.158G>A变异的致病性及基因型-表型相关性分析

    杨佩颖孙云王欣马定远...
    278-283页
    查看更多>>摘要：目的 探讨苯丙氨酸羟化酶(PAH)缺乏症相关的PAH基因c.158G>A变异的致病性以及与表型的相关性。 方法 回顾分析2016年7月至2021年6月南京医科大学附属妇产医院确诊的37例PAH缺乏症患儿的临床资料和基因检测结果。 结果 在37例患儿中，轻度高苯丙氨酸血症(HPA)共34例，其中33例检测到2处PAH变异(包括c.158G>A)且均为复合杂合子，1例检测到3处PAH变异，包括c.158G>A纯合变异及c.842＋2T>A杂合变异。3人为经典型苯丙酮尿症(PKU)，并携带3处PAH变异，在其中2例中c.158G>A与c.842＋2T>A呈顺式排列，基因型为c.[158G>A，842＋2T>A]/c.728G>A和c.[158G>A，842＋2T>A]/c.611A>G，在另1例中158G>A与c.722G>A呈顺式排列，基因型为c.[158G>A，c.722G>A]/c.728G>A。其中，c.158G>A变异对PAH的活性影响较小，与轻度HPA表型相关，可归类为"可能良性"变异，但患者的临床表型还与另一等位基因的变异类型有关。 结论 37例PAH缺乏症患儿遗传学研究提示，c.158G>A变异与其他致病变异呈顺式排列时，患者的临床表型主要取决于其余2个变异的致病性。 Objective To explore the pathogenicity and genotype-phenotype correlation of a c. 158G>A variant of phenylalanine hydroxylase (PAH) gene among patients with PAH deficiency. Methods Thirty seven children diagnosed with PAH deficiency at the Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University between July 2016 and June 2021 were selected as the study subjects. Clinical data and results of genetic testing were retrospectively analyzed. Results Among the 37 patients, mild hyperphenylalaninemia (HPA) was observed in 34 cases, two PAH variants (including c. 158G>A), which formed a compound heterozygous mutation genotype, were detected in 33 patients, and the remainder one was found to harbor threePAH variants, including homozygous c. 158G>A variants and a heterozygous c. 842+ 2T>A variant. Classical phenylketonuria (PKU) was observed in 3 patients, and threePAH variants were detected in each of them, including two with c. [158G>A, 842+ 2T>A]/c.728G>A and c. [158G>A, 842+ 2T>A]/c.611A>G, respectively, and one with c. [158G>A, c. 722G>A]/c.728G>A. The c. 158G>A variant has a minimal influence on thePAH activity and is associated with a mild HPA phenotype. The variant should thereby be classified as likely benign. Conclusion When the c. 158G>A variant and other pathogenic variants are arrangedin cis position, the ultimate phenotype will be determined by the pathogenicity of other variants.

    苯丙氨酸羟化酶PAH基因c．158G>A变异

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    SCN1A基因变异致遗传性癫痫伴热性惊厥附加症3个家系的临床及遗传学分析

    杨志刚王媛陈国洪宋丽芳...
    284-288页
    查看更多>>摘要：目的 探讨3个遗传性癫痫伴热性惊厥附加症(GEFS＋)家系的临床及基因变异特征。 方法 回顾性分析2020年1月至2021年12月就诊于郑州大学附属儿童医院的3例GEFS＋先证者及其家系成员的临床资料，对其进行全外显子组测序分析，并利用Sanger测序对候选变异进行验证。 结果 先证者1为3岁2月龄男性，表现为热性惊厥附加症，其父亲、2个姑姑、奶奶、姨奶、舅爷及外曾祖母均在1 ～ 2岁时有发热抽搐，6岁之后未再发作。先证者2为1岁4月龄男性，表现为复杂型热性惊厥，其母亲、舅舅及外祖母在5 ～ 6岁前均有发热、抽搐。先证者3为3岁11月龄男性，表现为热性惊厥附加症，其父亲、爷爷幼年均有发热、抽搐，7 ～ 8岁后未再发作。基因检测显示先证者1的SCN1A基因存在父源c.1613T>C杂合变异，先证者2的SCN1A基因存在母源c.2804A>G杂合变异，先证者3的SCN1A基因存在父源c.1271T>C杂合变异，上述变异均被评级为可能致病性变异(PM1＋PM2_Supporting＋PP1＋PP3＋PP4)。 结论 SCN1A基因c.1613T>C、c.2804A>G及c.1271T>C变异考虑为3个GEFS＋家系的遗传学病因。 Objective To analyze the clinical and genetic characteristics of three Chinese pedigrees affected with Genetic epilepsy with febrile seizures plus (GEFS+ ). Methods Three GEFS+ probands and their pedigree members presented at the Children′s Hospital of Zhengzhou University from January 2020 to December 2021 were selected as the study subjects. Clinical data of the pedigrees were collected. Whole exome sequencing was carried out for the probands, and Sanger sequencing was used to verify the candidate variants. Results Proband 1 was a 3-year-and-2-month-old male with febrile seizure plus. His father, two aunts, grandmother, aunt grandmother, uncle grandfather, and paternal great-grandmother also had onset of febrile seizures at 1 ~ 2 years of age with remission before 6 years old. Proband 2 was a 1-year-and-4-month-old male with complex febrile seizure. His mother, maternal uncle, and maternal grandmother also had febrile seizures before 5 ~ 6 years of age. Proband 3 was a 3-year-and-11-month-old male with febrile seizure plus. His father and grandfather also had febrile seizures plus with remission at 7 ~ 8 years of age. Genetic testing revealed that proband 1 had harbored a paternally derived heterozygous SCN1A: c. 1613T>C variant, proband 2 had harbored a maternally derived heterozygousSCN1A: c. 2804A>G variant, and proband 3 had harbored a paternally derived heterozygousSCN1A: c. 1271T>C variant. All of the three variants were predicted as likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (PM1+ PM2_Supporting+ PP1+ PP3+ PP4). Conclusion The c. 1613T>C, c. 2804A>G and c. 1271T>C variants probably underlay the pathogenesis of GEFS+ in these pedigrees.

    癫痫遗传性癫痫伴热性惊厥附加症SCN1A基因基因变异

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    β-酮硫解酶缺乏症3例患儿的临床及遗传学分析

    吴雪李园陈琼毋盛楠...
    289-293页
    查看更多>>摘要：目的 探讨3例β-酮硫解酶缺乏症(BKTD)患儿的临床特征和基因变异。 方法 回顾性分析河南省儿童医院2018年1月至2022年10月诊治的3例BKTD患儿的临床表现、实验室检查及基因检测资料，分析其临床和基因变异特点。 结果 3例患儿均为男性，年龄为7 ～ 11个月，表现为外伤应激、感染后出现精神差、气促、呕吐、抽搐等，均存在重度代谢性酸中毒、血和尿中酮体升高、低血糖、血异戊烯酰肉碱和3-羟基异戊酰肉碱升高、尿2-甲基-3-羟基丁酸和甲基巴豆酰甘氨酸增多。基因检测提示患儿1的ACAT1基因存在c.1183G>T杂合变异与1个涉及ACAT1基因的大片段缺失(chr11：102980303_110501515)，患儿2的ACAT1基因存在c.121-3C>G与c.826＋5_826＋9delGTGTT复合杂合变异，患儿3的ACAT1基因存在c.928G>C与c.1142T>C复合杂合变异。患儿2与患儿3的4种变异均为已知的致病性或可能致病性变异。根据美国医学遗传学与基因组学学会变异相关指南，患儿1的c.1183G>T被评级为意义不明变异(PM2_Supporting＋PP3＋PP4)，11q22.3-11q23.1大片段缺失查询DGV正常人群拷贝数变异数据库未见收录，被评级为致病性拷贝数变异。 结论 ACAT1基因的变异考虑为3例BKTD患儿的遗传学病因。 Objective To explore the clinical features and genetic variants in three children suspected for β-ketothiolase deficiency (BKTD). Methods Clinical manifestations, laboratory examination and genetic testing of three children suspected for BKTD at Henan Children′s Hospital between January 2018 and October 2022 were collected, and their clinical and genetic variants were retrospectively analyzed. Results The children were all males with a age from 7 to 11 months. Their clinical manifestations have included poor spirit, shortness of breath, vomiting, convulsions after traumatic stress and/or infection. All of them had severe metabolic acidosis, elevated ketone bodies in blood and urine, hypoglycemia, with increased isoprenyl-carnitine and 3-hydroxyisovalyl-carnitine in the blood, and 2-methyl-3-hydroxybutyrate and methylprotaroyl glycine in the urine. All of them were found to harbor compound heterozygous variants of the ACAT1 gene, including c. 1183G>T and a large fragment deletion (11q22.3-11q23.1) in child 1, c. 121-3C>G and c. 826+ 5_826+ 9delGTGTT in child 2, and c. 928G>C and c. 1142T>C in child 3. The variants harbored by children 2 and 3 were known to be pathogenic or likely pathogenic. The heterozygous c. 1183G>T variant in child 1 was unreported previously and rated as a variant of unknown significance (PM2_Supporting+ PP3+ PP4) based on guidelines from the American College of Medical Genetics and Genomics. The large segment deletion in 11q22.3-11q23.1 has not been included in the DGV Database and was rated as a pathogenic copy number variation. Conclusion The variants of the ACAT1 gene probably underlay the pathogenesis of BKTD in these three children.

    乙酰CoAC-酰基转移酶β-酮硫解酶缺乏症低血糖酮症酸中毒2-甲基-3羟基丁酸ACAT1基因

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    脊髓性肌萎缩症2＋0型案例分析与胚胎植入前单基因病检测的临床应用

    李少英何健淳何文智冼嘉嘉...
    294-299页
    查看更多>>摘要：目的 探讨胚胎植入前单基因病检测在特殊的脊髓性肌萎缩症(SMA)2＋0型中的临床应用。 方法 回顾性分析2020年10月19日于广州医科大学附属第三医院就诊的1例特殊SMA家系资料。利用多重连接探针扩增技术和分子标签连锁分析对夫妇双方及其胎儿进行SMN1基因型的鉴定，并借助二代测序(NGS)、分子标签连锁分析以及染色体微阵列分析3种方法对该夫妇的11枚胚胎进行单体型分析和结果验证。 结果 明确了女方为特殊的SMN1[2＋0]携带型，产前诊断确定胎儿为SMA患者，最终通过行胚胎植入前单基因病遗传检测成功筛选出4枚未携带SMN1致病变异和X染色体缺失的胚胎。 结论 胚胎植入前单基因病遗传检测能够有效阻断上述SMA 2＋0型患者的特殊遗传变异的传递，为家系再生育提供指导。 Objective To explore the clinical application of preimplantation genetic testing for monogenic disorders (PGT-M) in an unique case with Spinal muscular atrophy (SMA) type 2+ 0. Methods A special SMA family presented at the Third Affiliated Hospital of Guangzhou Medical University on October 19, 2020 was selected as the study subject. Multiple ligation-dependent probe amplification (MLPA) and molecular tagging linkage analysis were carried out to identify the SMN1 genotype of the couple and their fetus. Subsequently, next-generation sequencing (NGS), molecular tagging linkage analysis, and chromosomal microarray analysis were employed to determine the haplotypes and validate the result of PGT-M on the 11 embryos derived for the couple. Results The female partner was identified as a carrier of the rare SMN1[2+ 0] variant, and prenatal diagnosis confirmed the fetus to be affected by SMA. Ultimately, PGT-M has successfully selected four embryos free from the pathogenic SMN1 variants and X chromosome deletion. Conclusion PGT-M can effectively prevent the transmission of rare genetic variants such as the SMA 2+ 0 subtype in the families. Above finding has provided guidance for genetic counseling and family planning for the couple.

    肌萎缩,脊髓性SMN1基因胚胎植入前单基因病遗传检测二代测序连锁分析

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    卷积神经网络在染色体分类中的应用研究

    徐玲玲周颖张莉超王振宇...
    300-305页
    查看更多>>摘要：目的 运用深度学习方法构建卷积神经网络(CNN)模型，实现中期染色体的自动分类，并评价模型染色体分类的准确率。 方法 收集2013年1月至2019年7月在宁波市妇女儿童医院出生缺陷防治实验室接受染色体病检查者的3 300份样本。共纳入3 300×46张染色体图片，其中70%作为训练集，30%作为测试集，用于构建CNN模型，随后应用952张中期染色体图片对建立的模型的染色体计数及"切割＋识别＋排列＋自动分析"的准确率进行评价。另取80张染色体图片资料，分别记录人和模型完成染色体分类的时间及准确率，综合评价模型的应用价值。 结果 CNN模型的分裂相计数准确率为61.81%，单条染色体的"切割＋识别＋排列＋自动分析"准确率为96.16%。CNN模型的分类耗时相对人工操作有了大幅度的提高，核型分析的准确率仅比遗传专科医师低3.58%。 结论 基于CNN构建的染色体分类模型具有较高的分类能力，能够减轻遗传医师在核型分析的过程中手动切割分类染色体的劳动强度，提高工作效率，因而具有较好的应用前景。 Objective To train a deep convolutional neural networks (CNN) using a labeled data set to classify the metaphase chromosomes and test its accuracy for chromosomal identification. Methods Three thousand and three hundred individuals undergoing surveillance for chromosomal disorders at the Laboratory for Comprehensive Prevention and Treatment of Birth Defects, Ningbo Maternal and Child Health Care Hospital from January 2013 to July 2019 were enrolled. A total of 3 300×46 chromosome images were included, of which 70% were used as the training set and 30% were used as the test set for the deep CNN. The accuracy of chromosome counting and "cutting + recognition + arrangement + automatic analysis" of the model were respectively evaluated. Another 80 images were collected to record the time and accuracy of chromosome classification by geneticists and the model, respectively, so as to assess the practical value of the model. Results The CNN model was used to count the chromosomes with an accuracy of 61.81%, and the "cutting + recognition + arrangement + automatic analysis" accuracy of the model was 96.16%. Compared with manual operation, the classification time of the CNN model has been greatly reduced, and its karyotyping accuracy was only 3.58% lower than that of geneticists. Conclusion The CNN model has a high performance for chromosome classification and can significantly reduce the work load involved with the segmentation and classification and improve the efficiency of chromosomal karyotyping, thereby has a broad application prospect.

    深度学习染色体分类染色体核型分析卷积神经网络

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    罕见鸟氨酸氨基甲酰转移酶缺乏症合并MECP2重复综合征一个家系的基因变异分析及产前诊断

    张庆华郝胜菊惠玲郑雷...
    306-311页
    查看更多>>摘要：目的 分析1例鸟氨酸氨基甲酰转移酶缺乏症(OTCD)合并MECP2重复综合征家系的基因变异特征，并为该家系提供产前诊断。 方法 回顾性分析2017年12月19日就诊于甘肃省妇幼保健院新生儿重症监护中心的1例患儿(先证者)及其家系成员的临床资料。高通量测序结合多重连接探针扩增(MLPA)技术对患儿进行致病性变异分析。短串联重复序列(STR)连锁分析、MLPA以及拷贝数变异测序(CNV-seq)对胎儿进行产前诊断。 结果 先证者为出生3 d的女婴，测序发现其携带OTC基因第7 ～ 9外显子杂合缺失。根据美国医学遗传学与基因组学会变异相关指南，该变异被评级为可能致病性变异(PVS1＋PM2_Supporting＋PP4)，与其急性脑病发作合并代谢异常(血氨显著升高、血瓜氨酸降低、尿乳清酸增高)的临床表现相符，确诊其为OTCD。产前诊断未发现胎儿携带与先证者相同的OTC基因缺失变异，但存在Xq28区重复，涵盖MECP2重复综合征的全部区域，且SRY(＋)，母亲及先证者均证实携带该重复。结合先证者存在X染色体失活的可能性，考虑先证者同时罹患OTCD与MECP2重复综合征，而胎儿为MECP2重复综合征男性患者。 结论 基因检测明确了OTCD合并MECP2重复综合征家系的致病变异，可为患者家庭的精准治疗、遗传咨询及再次生育提供依据。 Objective To explore the genetic basis for a Chinese pedigree affected with co-morbid Ornithine carbamoyl transferase deficiency (OTCD) and MECP2 duplication syndrome. Methods A proband who was admitted to the Neonatal Intensive Care Unit of Gansu Provincial Maternal and Child Health Care Hospital on December 19, 2017 was selected as the study subject. High-throughput sequencing and multiplex ligation-dependent probe amplification (MLPA) were carried out for her pedigree, and short tandem repeat-based linkage analysis and chromosome copy number variation sequencing (CNV-seq) were used for the prenatal diagnosis. Results The proband, a 3-day-old female, was found to harbor heterozygous deletion of exons 7-9 of the OTC gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PVS1+ PM2_Supporting+ PP4). The proband was diagnosed with OTCD, which was in keeping with her acute encephalopathy and metabolic abnormalities (manifesting as hyperammonemia, decreased blood citrulline, and increased urine orotic acid). Prenatal diagnosis was carried out for the subsequent pregnancy. The fetus did not harbor the exons 7-9 deletion of the OTC gene, but was found to carry a duplication in Xq28 region (which encompassed the whole region of MECP2 duplication syndrome) and was positive for the SRY sequence. The same duplication was also found in the proband and her mother. Considering the possible existence of X-chromosome inactivation, the proband was diagnosed with two X-linked recessive disorders including OTCD and MECP2 duplication syndrome, and the fetus was determined as a male affected with the MECP2 duplication syndrome. Conclusion Discoveries of the pathogenic variants underlying the OTCD and MECP2 duplication syndrome have enabled clinical intervention, treatment, genetic counseling and prenatal diagnosis for this pedigree.

    高氨血症鸟氨酸氨基甲酰转移酶缺乏症OTC基因产前诊断拷贝数变异MECP2重复综合征

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    涉及4条染色体复杂重排的临床诊断

    胡斌许欢欢徐亮龙洋...
    311页
    查看更多>>摘要：男性，年龄为23岁，因"未避孕未育3年"于2020年6月9日入院就诊。夫妻双方性生活正常，否认阳痿、早泄，无射精障碍且能手淫射精，否认泌尿、生殖道感染史及家族史。系非近亲婚配。否认吸毒史，否认有毒物及放射线接触史。本研究遵循的程序符合2013年新修订的《世界医学协会赫尔辛基宣言》要求，患者签署了临床研究知情同意书。体格检查：身高167 cm，体质量56 kg，胡须、阴毛分布正常，阴茎自然长度6 cm，尿道口及阴囊发育未见异常，双侧睾丸体积约15 mL，输精管可触及，双侧精索静脉无曲张。细胞遗传学检查：常规制备染色体，G显带，常规计数20个中期分裂相，选取5个分散良好的核型进行分析。患者染色体核型为46，XY，der(1)t(1；6)(p34；p12)t(1；9)(q31；p23)，der(6)t(1；6)(p34；p12)del(6)(q12q15)，der(9)t(1；9)(q32；p22)，der(21)ins(21；6)(q22.1；q12q15)(图1、2、3)。
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