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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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    SACS基因变异所致Charlevoix-Saguenay型痉挛性共济失调患儿1例的遗传学分析

    罗欢陈小璐饶雪逸沈亚君...
    558-562页
    查看更多>>摘要：目的 探讨1例常染色体隐性遗传Charlevoix-Saguenay型痉挛性共济失调(ARSACS)患儿的临床及SACS基因变异特征。 方法 分析2021年4月30日收治于四川大学华西第二医院的1例ARSACS患儿的临床资料，对患儿及其父母进行全外显子组测序(WES)以及Sanger测序家系验证。依照美国医学遗传学与基因组学学会(ACMG)相关指南，利用生物信息学软件对候选变异进行致病性评级。 结果 患儿为3岁3月龄女性，因"行走不稳1+年"就诊，主要表现为进行性加重的步态不稳，右侧肢体肌张力增高，下肢周围神经病变和视网膜神经纤维层增厚。WES检测提示其携带母源性SACS基因第1 ~ 10外显子杂合缺失，同时第10外显子区存在c.3328dupA新发杂合变异。根据ACMG相关指南，exon(1-10)del被评级为可能致病性变异(PVS1+PM2_Supporting)，c.3328dupA被评级为致病性变异(PVS1_Strong+PS2 +PM2_Supporting)，二者均未被正常人群数据库收录。 结论 患者SACS基因第10外显子c.3328dupA杂合变异以及第1 ~ 10外显子杂合缺失可能是患儿的遗传学病因。 Objective To explore the clinical feature and genetic variant of a child with autosomal recessive Charlevoix-Saguenay type spastic ataxia (ARSACS). Methods Clinical data of a child who was admitted to the West China Second Hospital of Sichuan University on April 30, 2021 was collected. Whole exome sequencing (WES) was carried out for the child and his parents. Candidate variants were verified by Sanger sequencing and bioinformatic analysis based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Results The child, a 3-year-and-3-month-old female, had a complain of "walking instability for over a year" . Physical and laboratory examination revealed progressive and aggravated gait instability, increased muscle tone of the right limbs, peripheral neuropathy of the lower limbs, and thickening of retinal nerve fiber layer. The results of WES revealed that she has harbored a maternally derived heterozygous deletion of exons 1 to 10 of the SACS gene, in addition with a de novo heterozygous c. 3328dupA variant in exon 10 of the SACS gene. Based on the ACMG guidelines, the exons 1-10 deletion was rated as likely pathogenic (PVS1+ PM2_Supporting), and the c. 3328dupA was rated as a pathogenic variant(PVS1_Strong+ PS2+ PM2_Supporting). Neither variant was recorded in the human population databases. Conclusion The c. 3328dupA variant and the deletion of exons 1-10 of the SACS gene probably underlay the ARSACS in this patient.

    共济失调常染色体隐性遗传SACS基因全外显子组测序学龄前儿童

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    MYRF基因新发变异致心脏-泌尿生殖综合征胎儿1例的遗传学分析

    孙海瑞张宏家何怡华梁程红...
    563-567页
    查看更多>>摘要：目的 探讨1例心脏-泌尿生殖综合征(CUGS)胎儿的临床特征及基因变异特点。 方法 选取2019年1月首都医科大学附属北京安贞医院胎儿心脏病母胎医学中心诊断的1例先天性心脏病胎儿为研究对象。收集胎儿的临床资料，应用低深度全基因组测序(CNV-seq)和家系全外显子组测序(trio-WES)技术对胎儿及其父母进行遗传学分析，对候选变异进行Sanger测序家系验证。 结果 胎儿超声心动图提示主动脉弓发育不良。trio-WES检测发现胎儿携带MYRF基因c.1792-2A>C剪接变异，其父母均为野生型；Sanger测序验证该变异为新发变异。根据美国医学遗传与基因组学学会(ACMG)相关指南，评估为可能致病性变异。CNV-seq检测未发现非整倍体或与胎儿表型相关的致病性拷贝数变异。结合胎儿的临床表型及遗传学检测结果，考虑诊断为CUGS。 结论 MYRF基因c.1792-2A>C新发剪接变异可能是导致胎儿心脏畸形的遗传学病因。本研究丰富了MYRF基因的致病变异谱。 Objective To explore the genetic basis for a fetus with Cardiac-urogenital syndrome (CUGS). Methods A fetus with congenital heart disease identified at the Maternal Fetal Medical Center for Fetal Heart Disease, Beijing Anzhen Hospital Affiliated to Capital Medical University in January 2019 was selected as the study subject. Clinical data of the fetus was collected. Copy number variation sequencing (CNV-seq) and trio-whole exome sequencing (trio-WES) were carried out for the fetus and its parents. Candidate variants were verified by Sanger sequencing. Results Detailed fetal echocardiographic examination had revealed hypoplastic aortic arch. The results of trio-WES revealed that the fetus has harbored a de novo splice variant of the MYRF gene (c.1792-2A>C), for which both parents were of the wild-type. Sanger sequencing confirmed the variant to bede novo. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic. CNV-seq has identified no chromosomal anomalies. And the fetus was diagnosed with Cardiac-urogenital syndrome. Conclusion The de novo splice variant of the MYRF gene probably underlay the abnormal phenotype in the fetus. Above finding has enriched the spectrum of MYRF gene variants.

    全外显子组测序先天性心脏缺陷心脏-泌尿生殖综合征胎儿MYRF基因

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    Ⅱ型Cornelia de Lange综合征胎儿1例的临床表型及致病变异分析

    黄海龙侯佳汝周阳子刘彩霞...
    568-571页
    查看更多>>摘要：目的 探讨1例疑似Ⅱ型Cornelia de Lange综合征(CdLS2)的引产胎儿的孕期影像学表现及致病基因变异。 方法 以2019年9月3日于中国医科大学附属盛京医院妇产科确诊的1例CdLS2胎儿为研究对象。收集胎儿的临床资料和家族史。胎儿引产后应用全外显子组测序筛选致病变异，用Sanger测序对其进行家系验证。 结果 孕33周影像学检查提示胎儿透明隔略增宽，胼胝体显示不清，额叶体积略小，皮质变薄，侧脑室融合畸形，羊水过多，胃泡偏小，消化道闭锁。全外显子组测序发现胎儿携带X染色体SMC1A基因的c.2076delA(p.Lys692Asnfs*27)杂合移码变异，其父母均未检出相同的变异。结合美国医学遗传学与基因组学学会(ACMG)相关指南变异判断为致病性。 结论 CdLS2胎儿的遗传学病因考虑为SMC1A基因c.2076delA变异。上述结果为其父母的遗传咨询及再生育风险评估提供了依据。 Objective To explore the prenatal ultrasonographic features and genetic basis for an abortus suspected for type Ⅱ Cornelia de Lange syndrome (CdLS2). Methods A fetus diagnosed with CdLS2 at the Shengjing Hospital Affiliated to China Medical University on September 3, 2019 was selected as the study subject. Clinical data of the fetus and family history was collected. Following induced labor, whole-exome sequencing was carried out on the abortus. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. Results Prenatal ultrasonography (33 weeks of pregnancy) has revealed multiple anomalies in the fetus, which included slightly widened cavity of septum pellucidum, blurred corpus callosum, slightly reduced frontal lobe volume, thin cortex, fusion of lateral ventricles, polyhydramnios, small stomach bubble, and digestive tract atresia. Whole exome sequencing has revealed a heterozygous c. 2076delA (p.Lys692Asnfs*27) frameshifting variant in the SMC1A gene, which was found in neither parent and was rated as pathogenic based on the guidelines of American College of Medical Genetics and Genomics (ACMG). Conclusion The CdLS2 in this fetus may be attributed to the c. 2076delA variant of the SMC1A gene. Above finding has provided a basis for genetic counseling and assessment of reproductive risk for this family.

    CorneliadeLange综合征SMC1A基因移码变异全外显子组测序

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    Walker-Warburg综合征胎儿1例的产前诊断

    马盼盼陈雪惠玲张庆华...
    572-576页
    查看更多>>摘要：目的 探讨1例Walker-Warburg综合征(WWS)胎儿的遗传学特征。 方法 选取2021年6月9日至甘肃省妇幼保健院确诊的1例WWS胎儿为研究对象，采集胎儿羊水及其父母和姐姐的外周血样，提取基因组DNA，进行trio-WES检测，用Sanger测序对候选变异进行家系验证。 结果 Trio-WES检测显示胎儿POMT2基因存在第4外显子c.471delC(p.F158Lfs*42)移码变异和第20外显子的c.1975C>T(p.R659W)错义变异，分别遗传自父亲和母亲。根据美国医学遗传学与基因组学学会(ACMG)相关指南分别判定为致病性变异(PVS1+PM2_Supporting+PP4)和可能致病性变异(PM2_Supporting+PM3+PP3_Moderate+PP4)。 结论 产前诊断中应用trio-WES检测可快速可靠的确诊WWS患儿，为临床决策发挥重要作用。同时，发现POMT1基因1种新变异，在国内外未见报道。扩充了POMT2基因致病变异谱，为疾病的临床诊断和遗传咨询提供理论依据。 Objective To explore the genetic etiology for a fetus with Walker-Warburg syndrome(WWS). Methods A fetus with WWS diagnosed at Gansu Provincial Maternity and Child Health Care Hospital in June 9, 2021 was selected as the study subject. Genomic DNA was extracted from amniotic fluid sample of the fetus and peripheral blood samples from its parents. Trio-Whole exome sequencing (trio-WES) was carried out. Candidate variants were verified by Sanger sequencing. Results The fetus was found to harbor compound heterozygous variants of the POMT2 gene, namely c. 471delC (p.F158Lfs*42) and c. 1975C>T (p.R659W), which were respectively inherited from its father and mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), they were respectively rated as pathogenic (PVS1+ PM2_Supporting+ PP4) and likely pathogenic (PM2_Supporting+ PM3+ PP3_Moderate+ PP4). Conclusion Trio-WES may be used for the prenatal diagnosis of WWS. The compound heterozygous variants of the POMT2 gene probably underlay the disorder in this fetus. Above finding has expanded the mutational spectrum of the POMT2 gene and enabled definite diagnosis and genetic counseling for the family.

    Walker-Warburg综合征POMT2基因脑积水侧脑室增宽生物信息学分析

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    遗传性痉挛性截瘫56型患儿1例的 CYP2U1基因变异分析

    张广宇李三松杨磊王明梅...
    577-581页
    查看更多>>摘要：目的 分析1例表现为遗传性痉挛性截瘫(HSP)患儿的临床表型与遗传学特征。 方法 选取在2020年8月10日因"发现双下肢尖足2年"于郑州大学第三附属医院就诊的1例HSP女性患儿作为研究对象，收集其相关临床资料。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)，对候选变异进行Sanger测序家系验证。利用生物信息学软件分析变异位点氨基酸序列的进化保守性。 结果 患儿为2岁10月龄女性，临床表现为下肢肌张力增高、尖足、认知语言落后。Trio-WES检测提示患儿CYP2U1基因(NM_183075.3)第2外显子存在父源的c.865C>T (p.Gln289*)和母源的c.1126G>A (p.Glu376Lys)复合杂合变异，其中c.1126G>A (p.Glu376Lys)位点的氨基酸序列在多个物种中高度保守。根据美国医学遗传学与基因组学学会相关指南，c.865C>T变异评级为可能致病变异(PVS1+PM2_Supporting)，c.1126G>A变异评级为临床意义不明变异(PM2_Supporting+PM3+PP3)。 结论 该患儿被确诊为CYP2U1基因变异所致的遗传性痉挛性截瘫56型。新变异的检出丰富了CYP2U1基因的变异谱。 Objective To analyze the clinical phenotype and genetic characteristics of a child with Hereditary spastic paraplegia (HSP). Methods A child with HSP who was admitted to the Third Affiliated Hospital of Zhengzhou University on August 10, 2020 due to discovery of tiptoeing for 2 years was selected as the study subject, and relevant clinical data was collected. Peripheral blood samples of the child and her parents were collected for the extraction of genomic DNA. And trio-whole exome sequencing (trio-WES) was carried out. Candidate variants were verified by Sanger sequencing. Bioinformatic software was used to analyze the conservation of variant sites. Results The child was a 2-year-and-10-month-old female with clinical manifestations including increased muscle tone of lower limbs, pointed feet, and cognitive language delay. Trio-WES results showed that she had harbored compound heterozygous variants of c. 865C>T (p.Gln289*) and c. 1126G>A (p.Glu376Lys) of theCYP2U1 gene. And the corresponding amino acid for c. 1126G>A (p.Glu376Lys) is highly conserved among various species. Based on guidelines from the American College of Medical Genetics and Genomics, the c. 865C>T was predicted as a pathogenic variant (PVS1+ PM2_Supporting), and c. 1126G>A was rated as a variant of uncertain significance (PM2_Supporting+ PM3+ PP3). Conclusion The child was diagnosed with HSP type 56 due to compound variants of the CYP2U1 gene. Above findings have enriched the mutation spectrum of the CYP2U1 gene.

    遗传性痉挛性截瘫CYP2U1基因全外显子组测序儿童

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    FLNA基因变异所致Melnick-Needles综合征胎儿1例的临床特征及遗传学分析

    邹竞慧张宜生刘燕薛爱娇...
    582-587页
    查看更多>>摘要：目的 探讨1例Melnick-Needles综合征(MNS)胎儿的临床及遗传学特征。 方法 选取2020年11月至宁波市妇女儿童医院确诊的1例MNS胎儿为研究对象。采集胎儿的临床资料，应用家系全外显子组测序(trio-WES)对胎儿及其父母进行致病性变异筛选，对候选变异进行Sanger测序家系验证。 结果 产前超声提示胎儿偏小、双侧股骨弯曲、脐膨出、单脐动脉，合并羊水过少。Trio-WES发现其携带FLNA基因c.3562G>A(p.A1188T)半合子错义变异，Sanger测序验证为母源性，胎儿父亲该位点为野生型。根据美国医学遗传学与基因组学学会(ACMG)相关指南，评估为可能致病性变异(PS4+PM2_Supporting+PP3+PP4)。 结论 FLNA基因c.3562G>A(p.A1188T)半合子变异可能为该MNS胎儿的遗传学病因。基因诊断有助于MNS的精准诊断，可为家系遗传咨询和再生育提供依据。 Objective To explore the clinical and genetic characteristics of a fetus with Melnick-Needles syndrome (MNS). Methods A fetus with MNS diagnosed at Ningbo Women and Children′s Hospital in November 2020 was selected as the study subject. Clinical data was collected. Pathogenic variant was screened by using trio-whole exome sequencing (trio-WES). Candidate variant was verified by Sanger sequencing. Results Prenatal ultrasonography of the fetus had shown multiple anomalies including intrauterine growth retardation, bilateral femur curvature, omphalocele, single umbilical artery, and oligohydramnios. Trio-WES revealed that the fetus has harbored hemizygous c. 3562G>A (p.A1188T) missense variant of theFLNA gene. Sanger sequencing confirmed that the variant was maternally derived, whilst its father was of a wild type. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PS4+ PM2_Supporting+ PP3+ PP4). Conclusion The hemizygous c. 3562G>A (p.A1188T) variant of theFLNA gene probably underlay the structural abnormalities in this fetus. Genetic testing can facilitate accurate diagnosis of MNS and provide a basis for genetic counseling for this family.

    Melnick-Needles综合征FLNA基因全外显子组测序错义变异胎儿

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    不良孕产相关异常染色体核型3例

    平慧李守霞郭红霞郭丽丽...
    587页
    查看更多>>摘要：男，29岁，结婚10年，妻子G4P2，先后生育1个7岁的脑瘫儿子和1个3岁表型与智力均正常的女儿，其后2次怀孕均于3个月时发生无明显诱因的胎停流产，孕期无特殊疾病与服药史。夫妻双方表型均正常，系非近亲结婚，无有害物质及放射线接触史，无不良嗜好，家族中其他成员无不良孕产史。患者有1个姐姐，已结婚并生育1健康男孩。夫妇双方生殖系统检查均未见异常，细胞遗传学检查提示患者的核型为46，XY，t(6；19)(6pter→6q25.3：：19q13.3→19qter；19pter→19q13.3：：6q25.3→6qter)(图1A)，其妻子核型未见异常。
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    13q21大片段缺失二家系胎儿的产前诊断和遗传学咨询研究

    解敏薛江阳张玉鑫刘颖文...
    588-592页
    查看更多>>摘要：目的 探讨2个13q21大片段缺失家系胎儿的产前诊断和遗传学咨询策略。 方法 选择2021年3月、2021年12月于宁波市妇女儿童医院产前诊断门诊确诊为胎儿13号染色体大片段缺失的2例单胎妊娠胎儿(胎儿1、2)为研究对象。2例胎儿母亲均完善羊水穿刺，对胎儿1、2进行染色体核型分析和染色体微阵列分析(CMA)，并采集胎儿父母的外周血样进行CMA检测，追溯胎儿异常染色体的来源。 结果 胎儿1、2的染色体核型均未见明显异常。CMA检测结果提示胎儿1、2分别携带母源性13q21.1q21.33区段11.935 Mb、父源性13q14.3q21.32区段10.995 Mb的杂合缺失。胎儿1、2的2个缺失的片段基因密度低，缺乏单倍剂量敏感基因，数据库检索缺乏有效数据，均判断为可能良性变异，2例胎儿父母均选择继续妊娠。 结论 本研究发现2个家系胎儿1、2的13q21区段缺失可能为良性变异，由于未进行足够长时间的随访研究，而且仅为病例研究，所以是否存在致病性尚没有充分证据，但是或许可为临床产前诊断和遗传咨询提供一定依据。 Objective To explore the strategies of prenatal diagnosis and genetic counseling for fetuses of two families with large deletions of 13q21. Methods Two singleton fetuses who were diagnosed with chromosome 13 microdeletions by non-invasive prenatal testing (NIPT) at Ningbo Women and Children′s Hospital in March 2021 and December 2021 respectively were selected as the study subjects. Chromosomal karyotyping and chromosomal microarray analysis (CMA) were carried on amniotic samples. Peripheral blood samples were collected from the two couples for CMA assay to determine the origin of abnormal chromosomes identified in the fetuses. Results The karyotypes of the two fetuses were both normal. CMA revealed that they have respectively harbored heterozygous deletions spanning 11.935 Mb at 13q21.1q21.33 and 10.995 Mb at 13q14.3q21.32, which were respectively inherited from their mother and father. Both deletions had low gene density and lacked haploinsufficient genes, and were predicted to be likely benign variants based on database and literature search. Both couples had opted to continue with the pregnancy. Conclusion The deletions of the 13q21 region in both families may be of benign variants. As the follow-up time was short, there was no sufficient evidence for the determination of pathogenicity, though our finding may still provide a basis for the prenatal diagnosis and genetic counseling.

    产前诊断13q21大片段缺失可能良性变异胎儿

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    新发46，X，der(X)t(X；Y)(q26；q11)胎儿1例的遗传学分析

    王永安章荣尹婷王志伟...
    593-597页
    查看更多>>摘要：目的 对1例新发46，X，der(X)t(X；Y)(q26；q11)胎儿进行产前遗传学分析。 方法 选取2021年5月22日就诊于连云港市妇幼保健院的1例孕妇作为研究对象。收集孕妇的临床资料，采集夫妇的外周静脉血样以及胎儿的脐血样本，进行常规的G显带核型分析。提取羊水DNA，对其进行染色体微阵列分析(CMA)，并对变异的致病性进行分析。 结果 孕25周超声检查提示胎儿为永存左上腔静脉，二、三尖瓣少量反流。G显带核型分析显示，胎儿Y染色体pter-q11片段易位至X染色体长臂q26处，孕妇夫妇核型均未见明显异常。CMA检测显示，胎儿X染色体长臂末端存在约21 Mb的缺失[arr[hg19]Xq26.3q28(133912218_154941869)×1]，Y染色体长臂存在约42 Mb的重复[arr[hg19]Yq11.221qter(17405918_59032809)×1]。结合DGV、OMIM、DECIPHER、ClinGen及PubMed等数据库的检索结果，根据美国医学遗传学与基因组学学会(ACMG)相关指南，判断上述Xq26.3q28缺失为致病性，Yq11.221qter重复为临床意义不明。 结论 Xq-Yq相互易位可能是胎儿的遗传学病因，预测可导致卵巢功能障碍与发育迟缓。联合应用G显带核型分析与CMA检测能够及时诊断胎儿染色体结构异常的类型与来源、区分平衡和不平衡易位，对孕妇妊娠结局的选择具有重要的参考价值。 Objective To carry out prenatal genetic testing for a fetus with de novo 46, X, der(X)t(X Y)(q26 q11). Methods A pregnant woman who had visited the Birth Health Clinic of Lianyungang Maternal and Child Health Care Hospital on May 22, 2021 was selected as the study subject. Clinical data of the woman was collected. Peripheral blood samples of the woman and her husband and umbilical cord blood of the fetus were collected and subjected to conventional G-banded chromosomal karyotyping analysis. Fetal DNA was also extracted from amniotic fluid sample and subjected to chromosomal microarray analysis (CMA). Results For the pregnant women, ultrasonography at 25th gestational week had revealed permanent left superior vena cava and mild mitral and tricuspid regurgitation. G-banded karyotyping analysis showed that the pter-q11 segment of the fetal Y chromosome was connected to the Xq26 of the X chromosome, suggesting a Xq-Yq reciprocal translocation. No obvious chromosomal abnormality was found in the pregnant woman and her husband. The CMA results showed that there was approximately 21 Mb loss of heterozygosity at the end of the long arm of the fetal X chromosome [arr[hg19]Xq26.3q28(133912218_154941869)×1], and 42 Mb duplication at the end of the long arm of the Y chromosome [arr[hg19]Yq11.221qter(17405918_59032809)×1]. Combined with the search results of DGV, OMIM, DECIPHER, ClinGen and PubMed databases, and based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the deletion of arr[hg19]Xq26.3q28(133912218_154941869)×1 region was rated as pathogenic, and the duplication of arr[hg19]Yq11.221qter(17405918_59032809)×1 region was rated as variant of uncertain significance. Conclusion The Xq-Yq reciprocal translocation probably underlay the ultrasonographic anomalies in this fetus, and may lead to premature ovarian insufficiency and developmental delay after birth. Combined G-banded karyotyping analysis and CMA can determine the type and origin of fetal chromosomal structural abnormalities as well as distinguish balanced and unbalanced translocations, which has important reference value for the ongoing pregnancy.

    染色体微阵列分析G显带核型分析Xq-Yq相互易位产前诊断

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    以先天性甲状腺功能减退为表现的14q12q13.3微缺失综合征患儿1例的临床及遗传学分析

    汪洁李洪娟袁淑华孙学梅...
    598-603页
    查看更多>>摘要：目的 分析1例以先天性甲状腺功能减退症(CH)为表现的14q12q13.3微缺失综合征患儿的临床表型与遗传学病因。 方法 以1例因先天性甲状腺功能减退就诊于临沂市人民医院的新生儿作为研究对象，对其进行全外显子组测序(WES)、深度基因组拷贝数变异(CNV)和染色体微阵列分析(CMA)，分析其临床资料并进行文献复习。 结果 患儿于新生儿期起病，主要表现为特殊面容、外阴水肿、肌张力低下、精神运动发育迟缓、反复呼吸道感染伴喉喘鸣和喂养困难等，实验室检测显示甲状腺功能减退。WES和深度基因组CNV分析检测提示患儿染色体14q12q13.3区可能存在拷贝数缺失，CMA证实其14q12q13.3区(32649595_36769800)存在4.12 Mb的片段缺失，共涉及22个基因，包含CH的致病基因NKX2-1，患儿父母均未发现同样的片段缺失。 结论 综合其临床表型及基因检测的结果，确诊患儿为14q12q13.3微缺失综合征。 Objective To analyze the clinical phenotype and genetic etiology for a child featuring congenital hypothyroidism(CH). Methods Whole exome sequencing(WES), copy number variation(CNV) sequencing and chromosomal microarray analysis(CMA) were carried out for a newborn infant who had presented at Linyi People′s Hospital for CH. Clinical data of the child was analyzed, in addition with a literature review. Results The main characteristics of the newborn infant had included peculiar face, vulvar edema, hypotonia, psychomotor retardation, recurrent respiratory tract infection with laryngeal wheezing and feeding difficulties. Laboratory test indicated hypothyroidism. WES suggested a CNV deletion on chromosome 14q12q13. CMA further confirmed a 4.12 Mb deletion at chromosome 14q12q13.3 (32649595_36769800), which has encompassed 22 genes including NKX2-1, the pathogenic gene for CH. The same deletion was found in neither of her parents. Conclusion Through the analysis of clinical phenotype and genetic variant, the child was diagnosed with 14q12q13.3 microdeletion syndrome.

    先天性甲状腺功能减退症14q12q13.3微缺失综合征NKX2-1基因

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