首页期刊导航|中华医学遗传学杂志
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。
正式出版
收录年代

    早期发病的神经发育障碍伴非自主运动患儿1例的遗传学分析及文献复习

    胡文静方红军唐静文周珍...
    385-389页
    查看更多>>摘要：目的 探讨1例早期发病的神经发育障碍伴非自主运动(NEDIM)患儿的临床特征与遗传学病因。 方法 选取2020年10月8日于湖南省儿童医院神经内科就诊的1例早期发病NEDIM患儿为研究对象。收集患儿的临床资料，抽取患儿及其父母的外周静脉血样，对患儿进行全外显子组测序(WES)，用Sanger测序对候选变异进行家系验证，并对其进行生物信息学分析。在中国知网(CNKI)、美国医学文摘数据库(PubMed)及谷歌学术等数据库中检索GNAO1基因c.626G>A变异相关的NEDIM病例报道，对患者的临床表型及GNAO1基因的变异情况进行总结。 结果 患儿为男性，3岁1月龄，临床表现为四肢不自主抖动、运动与语言发育迟缓。WES检测结果提示其携带GNAO1基因c.626G>A(p.Arg209His)杂合错义变异。经Sanger测序验证，患儿父母GNAO1基因均为野生型，提示患儿为新发变异。GNAO1基因c.626G>A(p.Arg209His)变异在HGMD及ClinVar数据库中已见报道。经dbSNP、ExAC及1000 Genomes等数据库检索，该变异均未见收录。SIFT、PolyPhen-2及Mutation Taster等在线软件预测结果均提示，该变异对编码蛋白产生有害影响。经UniProt数据库分析，该变异编码氨基酸在不同物种间高度保守；Modeller与PyMOL软件预测结果显示，该变异可能影响其编码蛋白Gαo蛋白的功能。根据美国医学遗传学与基因组学学会(ACMG)制订的《序列变异解释的标准和指南》，该变异被评级为致病性变异(PS2+PS1+PM1+PM2_Supporting+PP3)。 结论 GNAO1基因c.626G>A(p.Arg209His)变异可能为NEDIM患儿的遗传学病因，进一步丰富了GNAO1基因c.626G>A(p.Arg209His)变异的表型谱，为该病患儿临床诊断与遗传咨询提供参考依据。 Objective To explore the clinical phenotype and genetic basis of a child with early onset neurodevelopmental disorder with involuntary movement (NEDIM). Methods A child who presented at Department of Neurology of Hunan Children′s Hospital on October 8, 2020 was selected as the study subject. Clinical data of the child were collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents. Whole exome sequencing (WES) was carried out for the child. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. Relevant literature was searched from the CNKI, PubMed and Google Scholar databases to summarize the clinical phenotypes and genetic variants of the patients. Results This child was a 3-year-and-3-month boy with involuntary trembling of limbs and motor and language delay. WES revealed that the child has harbored a c. 626G>A (p.Arg209His) variant of theGNAO1 gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. The variant had been reported in HGMD and ClinVar databases, but not in the dbSNP, ExAC and 1000 Genomes databases. Prediction with SIFT, PolyPhen-2, and Mutation Taster online software suggested that the variant may be deleterious to the protein function. By UniProt database analysis, the encode amino acid is highly conserved among various species. Prediction with Modeller and PyMOL software indicated that the variant may affect the function of GαO protein. Based on the guideline of the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic. Conclusion The GNAO1 gene c. 626G>A(p.Arg209His) variant probably underlay the NEDIM in this child. Above finding has expanded the phenotypic spectrum ofGNAO1 gene c. 626G>A (p.Arg209His) variant and provided a reference for clinical diagnosis and genetic counseling.

    神经发育障碍运动障碍GNAO1基因基因检测

      原文链接:
    • 万方数据

    青少年起病的伴基底节区和小脑萎缩的低髓鞘化脑白质营养不良患者1例的 TUBB4A基因变异分析

    应子璇程曦许晓泉马志...
    390-394页
    查看更多>>摘要：目的 探讨1例青少年起病的伴基底节区和小脑萎缩的低髓鞘化脑白质营养不良(H-ABC)患者的临床特征与遗传学病因。 方法 选取2018年3月于南京医科大学第一附属医院就诊的1例H-ABC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，用全外显子组测序(WES)对患者进行检测，对候选变异进行Sanger测序家系验证和致病性分析。 结果 患者为31岁男性，表现为发育迟缓、认知下降及步态异常等。WES检测结果提示其TUBB4A基因存在c.286G>A杂合变异，Sanger测序结果显示患者父母均未携带该变异。经SIFT在线软件分析，该变异位点编码的氨基酸具有高度的进化保守性。该变异已被人类基因突变数据库(HGMD)收录，人群携带频率低。经PyMOL软件构建3D结构显示，该变异对编码蛋白结构及功能可能产生有害的影响。根据美国医学遗传学与基因组学学会(ACMG)相关指南，该变异被评级为可能致病性变异(PS2+PM2_Supporting)。 结论 TUBB4A基因c.286G>A(p.Gly96Arg)变异可能是H-ABC患者的遗传学病因。上述发现进一步丰富了TUBB4A基因的变异谱，为患者的早期确诊提供了依据。 Objective To explore the clinical characteristics and genetic etiology of a patient with adolescent-onset hypomyelinated leukodystrophy with atrophy of basal ganglia and cerebellum (H-ABC). Methods A patient who was diagnosed with H-ABC in March 2018 at the First Affiliated Hospital of Nanjing Medical University was selected as the study subject. Clinical data was collected. Peripheral venous blood samples of the patient and his parents were collected. The patient was subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. Results The patient, a 31-year-old male, had manifested with developmental retardation, cognitive decline and abnormal gait. WES revealed that he has harbored a heterozygous c. 286G>A variant of theTUBB4A gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. Analysis with SIFT online software indicated the amino acid encoded by this variant is highly conserved among various species. This variant has been recorded by the Human Gene Mutation Database (HGMD) with a low population frequency. The 3D structure constructed by PyMOL software showed that the variant has a harmful effect on the structure and function of the protein. According to the guidelines formulated by the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic. Conclusion The c. 286G>A (p.Gly96Arg) variant of theTUBB4A gene probably underlay the hypomyelinating leukodystrophy with atrophy of basal ganglia and cerebellum in this patient. Above finding has enriched the spectrum of TUBB4A gene variants and enabled early definitive diagnosis of this disorder.

    低髓鞘化脑白质营养不良基底节区和小脑萎缩TUBB4A基因新发变异

      原文链接:
    • 万方数据

    MFSD8变异所致的成人起病的神经元蜡样脂褐质沉积症7型患者1例的临床特征及遗传学分析

    贺爽陈帅彭越樊晓蕊...
    395-401页
    查看更多>>摘要：目的 探讨1例成人起病的神经元蜡样脂褐质沉积症7型(CLN7)患者的临床表型及基因变异特点。 方法 选择2021年6月于河南省人民医院被确诊为CLN7女性患者为研究对象。采用回顾性分析方法，对该例患者的临床病例资料、辅助检查及基因检测结果进行分析。 结果 患者年龄为39岁，其主要临床表现为进行性视力下降、癫痫、共济失调和轻度认知减退；其神经影像学检查结果显示以小脑为主的全脑萎缩；眼底照相显示视网膜色素变性(RP)；皮肤组织病理学活检可见腺体外周间质细胞较多的脂褐素颗粒沉积。全外显子组测序(WES)提示患者MFSD8基因存在c.1444C>T(p.R482*)和c.104G>A(p.R35Q)复合杂合变异，其中c.1444C>T为已被文献报道的致病性无义变异，而c.104G>A为迄今尚未见报道的错义变异，Sanger测序显示患者的女儿、儿子及患者兄长分别携带c.1444C>T(p.R482*)、c.104G>A(p.R35Q)、c.104G>A(p.R35Q)变异，符合CLN7常染色体隐性遗传致病特点。 结论 本研究发现迄今发病年龄最晚的CLN7病例，临床特征为成年期起病的多系统受累，小脑萎缩及RP可进一步提示诊断，MFSD8基因的c.1444C>T(p.R482*)和c.104G>A(p.R35Q)复合杂合变异可能为该患者的遗传学病因。 Objective To explore the clinical characteristics and genetic variants in a patient with adult-onset ceroid lipofuscinosis neuronal type 7 (CLN7). Methods A female patient diagnosed with CLN7 in Henan Provincial People′s Hospital in June 2021 was selected as the study subject. Clinical data, auxiliary examination and result of genetic testing were retrospectively analyzed. Results The patient, a 39-year-old female, has mainly presented progressive visual loss, epilepsy, cerebellar ataxia and mild cognitive decline. Neuroimaging analysis has revealed generalized brain atrophy, prominently cerebellum. Fundus photography has revealed retinitis pigmentosa. Ultrastructural skin examination has revealed granular lipofuscin deposits in the periglandular interstitial cells. Whole exome sequencing (WES) revealed that she has harbored compound heterozygous variants of the MSFD8 gene, namely c. 1444C>T (p.R482*) and c. 104G>A (p.R35Q). Among these, c. 1444C>T (p.R482*) was a well established pathogenic variant, while c. 104G>A (p.R35Q) was a missense variant unreported previously. Sanger sequencing confirmed that the daughter, son and elder brother of the proband have respectively carried heterozygous c. 1444C>T (p.R482*), c. 104G>A (p.R35Q), and c. 104G>A (p.R35Q) variants of the same gene. The family has therefore fit with the autosomal recessive inheritance pattern of the CLN7. Conclusion Compared with previously reported cases, this patient has the latest onset of the disease with a non-lethal phenotype. Her clinical features have involved multiple systems. Cerebellar atrophy and fundus photography may be indicative of the diagnosis. The c. 1444C>T (p.R482*) and c. 104G>A (p.R35Q) compound heterozygous variants of theMFSD8 gene probably underlay the pathogenesis in this patient.

    神经元蜡样脂褐质沉积症7型MFSD8基因小脑萎缩

      原文链接:
    • 万方数据

    Snijders Blok-Campeau综合征患儿1例的临床特征及基因变异分析

    李雨珂王潇娜刘梦源高杨...
    402-407页
    查看更多>>摘要：目的 探讨Snijders Blok-Campeau综合征(SBCS)患儿的临床表型和基因变异特点。 方法 选取2017年6月于河南省儿童医院被确诊为SBCS的1例患儿为研究对象。收集患儿的临床病例资料，采集患儿及其父母的外周血样提取基因组DNA，进行家系全外显子组测序(trio-WES)及基因组拷贝数变异(CNV)检测，针对可疑致病变异位点，应用Sanger测序进行家系验证。 结果 患儿主要临床表现为语言障碍、智力障碍和运动发育迟缓，伴特殊面容(前额宽、面部呈倒三角状、眉毛稀疏、眼距宽、眼裂小、鼻梁宽、面中部凹陷、上唇薄、尖下颌、耳位低且耳壳后旋)。trio-WES和Sanger测序结果提示患儿存在CHD3基因c.4073-2A>G杂合剪接变异，其父母均为野生型，CNV检测未发现致病性CNV。 结论 该SBCS患儿临床特征为语言和智力障碍、运动发育迟缓，伴特殊面容。CHD3基因剪接变异可能为导致该患儿罹患SBCS的遗传学病因。 Objective To analyze the clinical phenotype and genetic variant of a child with Snijders Blok-Campeau syndrome (SBCS). Methods A child who was diagnosed with SBCS in June 2017 at Henan Children′s Hospital was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and the extraction of genomic DNA, which was subjected to trio-whole exome sequencing (trio-WES) and genome copy number variation (CNV) analysis. Candidate variant was verified by Sanger sequencing of his pedigree members. Results The main clinical manifestations of the child have included language delay, intellectual impairment and motor development delay, which were accompanied with facial dysmorphisms (broad forehead, inverted triangular face, sparse eyebrows, widely spaced eyes, narrow palpebral fissures, broad nose bridge, midface hypoplasia, thin upper lip, pointed jaw, low-set ears and posteriorly rotated ears). Trio-WES and Sanger sequencing revealed that the child has harbored a heterozygous splicing variant of the CHD3 gene, namely c. 4073-2A>G, for which both of his parents were of wild-type. No pathogenic variant was identified by CNV testing. Conclusion The c. 4073-2A>G splicing variant of theCHD3 gene probably underlay the SBCS in this patient.

    SnijdersBlok-Campeau综合征CHD3基因神经发育障碍剪接变异儿童

      原文链接:
    • 万方数据

    智力障碍和小头畸形伴脑桥和小脑发育不全患儿2例的临床及遗传学分析

    祁娜杨科雷星星王凤阳...
    408-412页
    查看更多>>摘要：目的 探讨2例智力障碍和小头畸形伴脑桥和小脑发育不全(MICPCH)患儿的临床特征与遗传学病因。 方法 选取2019年4月至2021年12月期间于河南省人民医院就诊的2例MICPCH患儿为研究对象。收集患儿的临床资料，采集患儿及其父母的外周静脉血样和患儿1母亲的羊水样本，用全外显子组测序(WES)、微阵列比较基因组杂交(aCGH)与荧光定量PCR(qPCR)对2例患儿及其父母、患儿1母亲的胎儿进行检测，对候选变异进行致病性分析。 结果 患儿1为6岁女性，主要临床表现为运动与语言发育迟缓；患儿2为4岁半女性，主要临床表现为小头畸形与智力低下。WES检测结果显示患儿2的CASK基因第4 ~ 14外显子区域(chrX：41446160_41604854)存在158.7 kb重复，其父母均未见该变异，提示为新发变异；aCGH检测结果显示患儿1的CASK基因第3外显子区域(chrX: 41637892_41666665)存在29 kb缺失，其父母和母亲的胎儿均未见该变异，提示为新发变异；qPCR检测结果进一步证实了WES与aCGH的检测结果。CASK基因第3外显子区域(chrX: 41637892_41666665)缺失与第4 ~ 14外显子区域(chrX：41446160_41604854)重复在ExAC、1000 Genomes及gnomAD等数据库中均未见收录，根据美国医学遗传学与基因组学学会(ACMG)相关指南，二者均被评级为可能致病性变异(PS2+PM2_Supporting)。 结论 CASK基因第3外显子区(chrX: 41637892_41666665)的缺失与第4 ~ 14外显子区(chrX：41446160_41604854)的重复可能分别是2例患儿的遗传学病因。上述结果为患儿的确诊提供了依据。 Objective To explore the clinical features and genetic etiology of two children with intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia (MICPCH). Methods Two children with MICPCH who were presented at the Henan Provincial People′s Hospital between April 2019 and December 2021 were selected as the study subjects. Clinical data of the two children were collected, along with peripheral venous blood samples of them and their parents, and amniotic fluid sample of the mother of child 1. Whole exome sequencing (WES), array-comparative genomic hybridization (aCGH) and quantitative PCR (qPCR) were carried out for the children, their parents and the fetus. The pathogenicity of candidate variants were evaluated. Results Child 1 was a 6-year-old girl featuring motor and language delay, whilst child 2 was a 4.5-year-old girl mainly featuring microcephaly and mental retardation. WES revealed that child 2 has harbored a 158.7 kb duplication in Xp11.4 (chrX: 41446160_41604854), which has encompassed exons 4~14 of the CASK gene. The same duplication was not found in either of her parents. aCGH revealed that child 1 has harbored a 29 kb deletion at Xp11.4 (chrX: 41637892_41666665), which encompassed exon 3 of the CASK gene. The same deletion was not found in either of her parents and the fetus. The above results were confirmed by qPCR assay. Above deletion and duplication were not found in the ExAC, 1000 Genomes and gnomAD databases. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as likely pathogenic (PS2+ PM2_Supporting). Conclusion The deletion of exon 3 and duplication of exons 4~14 of the CASK gene probably underlay the pathogenesis of MICPCH in these two children, respectively.

    智力障碍CASK基因全外显子组测序微阵列比较基因组杂交

      原文链接:
    • 万方数据

    FDXR变异致线粒体F-S病患儿1例的临床表型及基因变异分析

    胡文静凌秀昕方红军唐静文...
    413-418页
    查看更多>>摘要：目的 分析1例疑似线粒体F-S病患儿的临床表型及基因型特征，明确其致病原因，为临床诊断提供依据。 方法 选取2020年11月5日于湖南省儿童医院神经内科就诊的1例线料体F-S病患儿为研究对象。对患儿进行全外显子组测序(WES)，应用生物信息学分析筛选致病性变异，并对核心家系成员采用Sanger测序分析变异来源。 结果 基因检测发现患儿的FDXR基因存在c.310C>T(p.R104C)和c.235C>T(p.R79C)复合杂合变异，分别源自其父亲与母亲。经检索HGMD、PubMed、1000 Genomes及dbSNP等数据库，2个变异位点均为新变异。经不同生物学信息分析软件进行变异位点致病性预测，结果均提示有害。 结论 多系统受累时需警惕线粒体疾病，FDXR基因复合杂合变异可能为本例患儿的致病原因。上述发现丰富了FDXR基因致线粒体F-S病的变异谱，并提示全外显子组基因检测对线粒体F-S病诊断的辅助意义。 Objective To analyze the clinical phenotype and genetic variants of a child suspected for mitochondrial F-S disease. Methods A child with mitochondrial F-S disease who visited Department of Neurology, Hunan Provincial children′s Hospital on November 5, 2020 was selected as research subject of this study. Clinical data of the child was collected. The child was subjected to whole exome sequencing (WES). Bioinformatics tools were used to analyze the pathogenic variants. Candidate variants were verified by Sanger sequencing of the child and her parents. Results WES revealed that the child has harbored compound heterozygous variants of the FDXR gene, namely c. 310C>T (p.R104C) and c. 235C>T (p.R79C), which were inherited from her father and mother, respectively. Neither variant has been reported in HGMD, PubMed, 1000 Genomes, and dbSNP databases. Both of the variants have been suggested as deleterious according to the prediction results from different bioinformatics analysis software. Conclusion Mitochondrial diseases should be suspected for patients with multiple system involvement. The compound heterozygous variants of the FDXR gene probably underlay the disease in this child. Above finding has enriched the spectrum of FDXR gene mutations underlying mitochondrial F-S disease. WES can facilitate the diagnosis of mitochondrial F-S disease at the molecular level.

    FDXR基因线粒体F-S病基因变异儿童

      原文链接:
    • 万方数据

    46，XX，t(2；9)(p25.1；q22)，t(5；11)(p15.1；p15)复杂染色体重排1例

    郭红霞平慧郝润英李守霞...
    418页
    查看更多>>摘要：患者 女，30岁，G2P0，2021年2月因"2次胚胎停育"就诊于邯郸市中心医院，超声及其他相关生殖检查均未发现明显异常。丈夫年龄为29岁，常规检查夫妇双方的生殖系统未见明显异常，夫妇双方表型及智力均无明显异常，系非近亲结婚，否认有毒有害物质和放射线接触史，无不良嗜好。患者有1个姐姐与1个弟弟，均已结婚并生育1儿1女，表型均无明显异常。本研究通过了邯郸市中心医院伦理委员会的审查(210156)，患者及其家属均签署了临床研究知情同意书。细胞遗传学检查：患者染色体核型为46，XX，t(2；9；5；11)(9qter→9q22：：2p25.1→2qter 9pter→9q22：：2p25.1→2pter；11pter→11p15：：5p15.1→5qter 5pter→5p15.1：：11p15→11qter)(图1)。其丈夫染色体核型未见异常，其父母、姐姐及弟弟未做染色体检查。
      原文链接:
    • 万方数据

    痉挛性截瘫30型一个家系的 KIF1A基因变异分析

    许钢李建伟邓展进夏元...
    419-422页
    查看更多>>摘要：目的 探讨1例遗传性痉挛性截瘫30型(HSP30)家系的遗传学病因。 方法 以2021年8月就诊于山西医科大学第二医院的1例先证者以及家系成员为研究对象，对其进行全外显子组测序，并对候选变异进行Sanger测序家系验证。 结果 先证者携带KIF1A基因第3外显子c.110T>C(p.I37T)杂合变异，造成第37位的异亮氨酸替换为苏氨酸，可能影响其蛋白质产物的功能。先证者的父母、哥哥和姐姐均未携带相同的变异，提示其为新发变异。根据美国医学遗传学与基因组学学会(ACMG)相关指南，判断该变异为可能致病性变异(PM2_Supporting+PP3+PS2)。 结论 KIF1A基因c.110T>C变异可能是该先证者的遗传学病因。 Objective To explore the genetic basis for a Chinese pedigree affected with hereditary spastic paraplegia type 30 (HSP30). Methods A proband presented at the Second Hospital of Shanxi Medical University in August 2021 was selected as the study subject. The proband was subjected to whole exome sequencing, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. Results The proband was found to have harbored a heterozygous c. 110T>C variant in exon 3 of theKIF1A gene, which can cause substitution of isoleucine by threonine at position 37 (p.I37T) and alter the function of its protein product. The same variant was not found in his parents, elder brother and elder sister, suggesting that it has a de novo origin. Based on the guidelines of the American College of Medical Genetics and Genomics(ACMG), the variant was rated as likely pathogenic (PM2_Supporting+ PP3+ PS2). Conclusion The c. 110T>C variant of theKIF1A gene probably underlay the HSP30 in the proband. Above finding has enable genetic counseling for this family.

    KIF1A基因遗传性痉挛性截瘫错义变异

      原文链接:
    • 万方数据

    假肥大型肌营养不良性腺嵌合体七个家系的遗传学分析及生殖干预

    高伯笛杨晓文胡晓何文斌...
    423-428页
    查看更多>>摘要：目的 探讨7个假肥大型肌营养不良(DMD)性腺嵌合体家系的遗传学病因。 方法 选择2014年9月至2022年3月就诊于中信湘雅生殖与遗传专科医院的7个DMD性腺嵌合体家系为研究对象。收集家系的临床资料，应用胚胎植入前单基因遗传学检测(PGT-M)对家系6先证者的母亲进行助孕，采集7个家系的先证者、先证者母亲及其他患者的外周静脉血样、家系1 ~ 4胎儿的羊水、家系6体外培养胚胎的细胞，提取基因组DNA，用多重连接探针扩增(MLPA)对DMD基因进行检测，对家系1 ~ 3、5 ~ 6先证者、其他患者、胎儿、体外培养胚胎进行基于短串联重复序列(STR)/单核苷酸多态性(SNP)的单体型分析。 结果 MLPA检测结果显示，家系1 ~ 4、5、7的先证者与胎儿/先证者弟弟存在相同的DMD基因变异，其母亲DMD基因均未见异常；家系6的先证者仅与1枚体外培养胚胎(共9枚)存在相同的DMD基因变异，其母亲与通过PGT-M成功助孕胎儿的DMD基因均未见异常。STR单体型分析结果显示家系1 ~ 3、5的先证者与胎儿/先证者弟弟均遗传了相同的母源X染色体；SNP单体型分析结果显示，家系6先证者仅与1枚体外培养的胚胎(共9枚)继承了相同的母源X染色体。家系1胎儿与家系6中PGT-M助孕成功胎儿出生后随访均健康，家系2 ~ 3先证者的母亲选择了引产。 结论 基于STR/SNP的单体型分析是判断性腺嵌合体的有效方法，对生育过DMD基因变异患儿而外周血基因型正常的女性应考虑性腺嵌合体风险，再次妊娠时建议进行产前诊断与生殖干预，避免缺陷患儿的出生。 Objective To explore the genetic basis for 7 families with gonadal mosaicism for Duchenne muscular dystrophy (DMD). Methods For the 7 families presented at the CITIC Xiangya Reproductive and Genetic Hospital from September 2014 to March 2022, clinical data were collected. Preimplantation genetic testing for monogenic disorders (PGT-M) was carried out for the mother of the proband from family 6. Peripheral venous blood samples of the probands, their mothers and other patients from the families, amniotic fluid samples from families 1 ~ 4 and biopsied cells of embryos cultured in vitro from family 6 were collected for the extraction of genomic DNA. Multiplex ligation-dependent probe amplification (MLPA) was carried out for the DMD gene, and short tandem repeat (STR)/single nucleotide polymorphism (SNP)-based haplotypes were constructed for the probands, other patients, fetuses and embryos. Results The results of MLPA showed that the probands and the fetuses/probands′ brothers in families 1 ~ 4, 5, 7 had carried the same DMD gene variants, whilst the probands′ mothers were all normal. The proband in family 6 carried the same DMD gene variant with only 1 embryo (9 in total) cultured in vitro, and the DMD gene of the proband′s mother and the fetus obtained through the PGT-M were normal. STR-based haplotype analysis showed that the probands and the fetuses/probands′ brothers in families 1 ~ 3 and 5 have inherited the same maternal X chromosome. SNP-based haplotype analysis showed that the proband from family 6 has inherited the same maternal X chromosome with only 1 embryo (9 in total) cultured in vitro. The fetuses in families 1 and 6 (via PGT-M) were both confirmed to be healthy by follow up, whilst the mothers from families 2 and 3 had chosen induced labor. Conclusion Haplotype analysis based on STR/SNP is an effective method for judging gonad mosaicism. Gonad mosaicisms should be suspected for women who have given births to children with DMD gene variants but with a normal peripheral blood genotype. Prenatal diagnosis and reproductive intervention may be adapted to reduce the births of further affected children in such families.

    杜氏肌营养不良性腺嵌合体DMD基因多重连接探针扩增单体型分析

      原文链接:
    • 万方数据

    46，XX，t(4；12；20)(p15.2；p11.1；p13.1)复杂型平衡易位伴复发性流产1例

    倪蓉梁健吕述彦赵超...
    428页
    查看更多>>摘要：患者 女，27岁，2017年8月因"2次生化妊娠，1次早孕期胚停"于南京医科大学附属淮安第一医院就诊，此次孕71 d发生胚停(孕45 d检查胚芽、胎心未见异常)。体格检查：身高为162 cm，体质量为54 kg，表型、第二性征发育、智力均无明显异常。超声检查提示子宫大小正常、形态规则。内分泌检测：雌二醇、卵泡生成素、促黄体生成素、睾酮、垂体泌乳素均在正常参考值范围。
      原文链接:
    • 万方数据