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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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    SERPINC1基因变异所致遗传性抗凝血酶缺陷症家系的临床表型和遗传学分析

    陈迎迎姚雅婷李婷舒旷怡...
    312-316页
    查看更多>>摘要：目的 分析1个遗传性抗凝血酶(AT)缺陷症家系的临床表型及遗传学特征。 方法 回顾性分析2020年6月"因反复多部位形成静脉血栓"就诊于温州医科大学附属第二医院的1对AT先证者及其家系成员的临床资料。用STA-R全自动血凝分析仪检测先证者及家系成员血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)、凝血酶时间(TT)；用发色底物法和免疫散色比浊法检测先证者及其家系成员血浆AT活性(AT: A)和AT抗原(AT: Ag)。用PCR扩增先证者及家系成员抗凝血酶基因SERPINC1的所有外显子及侧翼序列，测序并寻找变异位点；采用生物信息学预测软件对蛋白质功能的影响和蛋白质构象的改变进行分析。 结果 先证者(Ⅱ2、Ⅱ10)及其兄弟(Ⅱ5)和儿子(Ⅲ1、Ⅲ8)的PT、APTT、FIB及TT均在正常范围，而AT: A和AT: Ag明显下降，分别为34%、57%、56%、48%、53%和13.51、13.44、18.39、17.36、17.71 mg/dL，其余家系成员均在正常范围。先证者及家系成员测序结果显示均携带SERPINC1基因第5外显子c.851T>C(p.Met284Thr)杂合错义变异；生物信息学软件预测提示该变异可导致c.851位点编码氨基酸的氢键改变，影响蛋白质的结构。根据美国医学遗传学与基因组学学会变异评级标准指南，该变异评级为致病性变异(PS1＋PM1＋PM5＋PP1＋PP4)。 结论 先证者及其他患者家系成员被确诊为Ⅰ型遗传性AT缺陷症患者，SERPINC1基因c.851T>C(p.Met284Thr)变异是其遗传学病因。 Objective To analyze the clinical phenotype and genetic characteristics of a Chinese pedigree affected with Hereditary antithrombin deficiency. Methods A pedigree diagnosed at the the Second Affiliated Hospital of Wenzhou Medical University, Yuying Children’s Hospital in June, 2020 was selected as the study subject. Plasma prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and thrombin time (TT) of the probands and their pedigree members were determined using a STA-R automatic coagulation analyzer. Antithrombin activity (AT: A) and antithrombin antigen (AT: Ag) in plasma were determined with chromogenic substrate and immunonephelometry assays. All exons and flanking sequences of the anticoagulant protein gene SERPINC1 were amplified by PCR and subjected to Sanger sequencing. Candidate variants were verified with bioinformatic tools (PolyPhen-2, SIFT, Mutation Taster and PYMOL) to explore their effect on the function and structural conformation of the protein. Results The probands (Ⅱ2, Ⅱ10), their brother (Ⅱ5) and sons (Ⅲ1, Ⅲ8) had shown normal PT, APTT, FIB, and TT, but significantly decreased AT: A and AT: Ag, with their levels being 34%, 57%, 56%, 48%, 53% and 13.51 mg/dL, 13.44 mg/dL, 18.39 mg/dL, 17.36 mg/dL, 17.71 mg/dL, respectively. The remaining pedigree members had normal values. Sanger sequencing revealed that the probands and all affected pedigree members had harbored a heterozygous c. 851T>C (p.Met284Thr) missense variant in exon 5 of theSERPINC1 gene. Bioinformatic analysis and simulation suggested that the variant has resulted in alteration of hydrogen bonds at the c. 851 position, which may affect the structure of the protein. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PS1+ PM1+ PM5+ PP1+ PP4). Conclusion The probands and other affected members were all diagnosed with type I hereditary AT deficiency, for which the c. 851 T>C (p.Met284Thr) variant of theSERPINC1 gene may be accountable.

    血液凝集障碍,遗传性遗传性抗凝血酶缺陷症SERPINC1基因基因变异

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    Ⅰ型神经纤维瘤病一个家系及散发病例1例的 NF1基因变异分析

    赵小燕周昆丽张启国蔡良奇...
    317-321页
    查看更多>>摘要：目的 对Ⅰ型神经纤维瘤病(NF1)1个家系和1例散发病例的NF1基因进行变异分析，探讨遗传学病因。 方法 回顾性分析2022年10月22日于厦门大学附属第一医院就诊的1个NF1家系及另1例散发NF1患儿的临床资料，提取患者外周血基因组DNA进行临床全外显子组捕获和测序，确定候选基因变异位点，针对变异位点进行Sanger测序验证。 结果 NF1家系中，先证者及其母亲与妹妹均携带NF1基因第25外显子c.3251delC变异，先证者父亲未携带该变异；散发NF1病例携带NF1基因第32外显子c.4312_4314delGAA变异，其父母均未携带该变异。根据美国医学遗传学与基因组学学会(ACMG)相关指南，c.3251delC与c.4312_4314delGAA均被评定为致病性变异(PVS1＋PS4_Supporting＋PM2_Supporting＋PP4；PS2＋PS4_Moderate＋PM2_Supporting＋PM4＋PP4) 结论 NF1基因c.3251delC与c.4312_4314delGAA变异可能分别为该家系及散发病例罹患NF1的致病原因。 Objective To explore the genetic basis for a Chinese pedigree and a sporadic case with Neurofibromatosis type 1 (NF1). Methods Clinical data of the pedigree and the sporadic case were collected. Genomic DNA was extracted from peripheral venous blood samples and subjected to whole exome sequencing. Candidate variants were validated by Sanger sequencing and bioinformatic analysis. Results All patients from the pedigree were found to harbor a c. 3251delC variant in exon 25 of the NF1 gene, whilst a c. 4312_4314delGAA variant was found in exon 32 of the NF1 gene in the sporadic case. Conclusion Variants of the NF1 gene may account for the occurrence of NF1 in this pedigree and sporadic case.

    基因检测Ⅰ型神经纤维瘤病NF1基因基因变异

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    全外显子组测序诊断由 TCOF1基因变异所致的Treacher-Collins综合征一个家系

    姜楠梁思颖苗艳李朔...
    322-325页
    查看更多>>摘要：目的 通过全外显子组测序(WES)探讨1个Treacher-Collins综合征(TCS)家系的遗传学病因。 方法 回顾性分析2020年2月5日于青岛大学附属妇女儿童医院就诊的1个TCS家系的临床资料，运用WES对先证者进行基因检测，对候选变异进行生物信息学分析，并通过Sanger测序进行家系验证。 结果 WES检测显示先证者携带TCOF1基因c.3337C>T杂合变异，Sanger测序显示其母亲和弟弟携带同样的杂合变异。依据美国医学遗传学与基因组学学会(ACMG)相关指南，该变异评定为致病性(PVS1＋PM2_Supporting＋PP4)。 结论 TCOF1：c.3337C>T可考虑为该TCS家系患病成员的致病原因。 Objective To explore the genetic etiology for a Chinese pedigree affected with Treacher-Collins syndrome (TCS) through whole exome sequencing (WES). Methods A TCS pedigree which was diagnosed at the Women and Children′s Hospital Affiliated to Qingdao University on February 5 2020 was selected as the study subject. Following collection of clinical data, WES was carried out. Candidate variant was validated through Sanger sequencing and bioinformatic analysis.. Results The WES results showed that the proband has harbored a heterozygous c. 3337C>T variant of theTCOF1 gene, and Sanger sequencing confirmed that his mother and brother also carried the same variant. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted as pathogenic (PVS1+ PM2_Supporting+ PP4). Conclusion The heterozygous c. 3337C>T variant of theTCOF1 gene probably underlay the pathogenesis of TCS in this pedigree.

    颅面骨发育不全Treacher-Collins综合征全外显子组测序技术TCOF1基因

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    Xq22.1q22.3杂合性缺失一个家系的X染色体失活分析及产前诊断

    陈雪君章卫国鞠翠钰
    326-330页
    查看更多>>摘要：目的 分析1个Xq22.1q22.3杂合性缺失家系中女性X染色体失活(XCI)偏倚及逃逸情况与表型的相关性。 方法 回顾性分析2021年11月10日于台州医院确诊的1个Xq22.1q22.3杂合性缺失家系的临床资料。对该家系胎儿羊水以及孕妇夫妇的外周血样进行G显带染色体分析和拷贝数变异测序(CNV-seq)，结合甲基化敏感性限制性核酸内切酶HpaⅡ消化前后PCR扩增雄性激素受体基因第1外显子CAG重复序列多态性的方法检测XCI。 结果 孕妇与胎儿的G显带核型均为46，X，del(X)(q22)，CNV-seq检测结果均为seq[hg19]del(X)(q22.1q22.3) chrX：g.100460000_105740000del，提示X染色体q22.1q22区存在5.28 Mb的拷贝数缺失，孕妇丈夫未见明显异常。XCI分析提示孕妇与胎儿的X染色体的活性比均为0∶100，携带Xq22.1q22.3缺失的X染色体完全失活，胎儿的失活染色体源自母亲。 结论 胎儿携带母源性失活的X染色体del(X)(q22)，携带者的表型与异常的X染色体活性密切相关。通过家系XCI分析结合孕妇临床表型有助于预测Xq22.1q22.3杂合性缺失家系女性胎儿的临床表型及预后，为遗传咨询提供依据。 Objective To explore the correlation between skewed X chromosome inactivation (XCI) and clinical phenotype of a Chinese pedigree with loss of heterozygosity at Xq22.1q22.3. Methods A pedigree diagnosed at Taizhou Hospital on November 10, 2021 was selected as the study subject. G-banded chromosomal karyotyping and copy number variation sequencing (CNV-seq) were carried out to analyze the amniotic fluid and peripheral blood samples from the couple. XCI was detected by PCR amplification of CAG repeats in exon 1 of androgen receptor gene before and after the digestion with methylation-sensitive restriction enzyme Hpa Ⅱ. Correlation between the genotype and clinical phenotype was analyzed. Results The karyotypes of the pregnant woman and the fetus were both determined as 46, X, del(X)(q22), and the result of CNV-seq was seq[hg19]del(X)(q22.1q22.3 ) chrX: g. 10046000_105740000del, suggesting that both had harbored a 5.28 Mb deletion on the X chromosome. No obvious abnormality was found in the husband. XCI analysis showed that the activity ratio of the two X chromosomes of the pregnant woman and her fetus was 0 : 100. The X chromosome harboring the q22.1q22.3 deletion was completely inactivated, and the inactivated X chromosome of the fetus was derived from its mother. Conclusion The fetus has harbored a maternally derived inactivated X chromosome del(X)(q22), and its phenotype is closely associated with the activity of the abnormal X chromosome. Pedigree XCI analysis combined with the clinical phenotype has facilitated recognition of the maternal phenotype and prognosis of female fetus with loss of heterozygosity at Xq22.1q22.3.

    产前诊断Xq22.1q22.3杂合性缺失X染色体失活基因型临床表型

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    Gitelman综合征2例患者的遗传学分析

    李志杰李文赵向宇李琳...
    331-334页
    查看更多>>摘要：目的 探讨2例Gitelman综合征(GS)患者的遗传学病因。 方法 选取分别于2022年1月和6月就诊于临沂市人民医院的2例GS患者作为研究对象进行回顾性研究。收集患者的血清检测血清电解质水平及电解质排泄量资料。采集患者外周血样提取基因组DNA进行全外显子组测序，并进行Sanger测序验证。 结果 患者1为27岁女性，血清钠、钾、氯及镁水平以及24 h尿氯、钙水平均低于参考值。基因检测发现其携带SLC12A3: c．1456G>A(p.D486N)和SLC12A3: c．179C>T(p.T60M)复合杂合变异，前者遗传自其母亲，为已报道致病性变异。患者2为4岁男性，血钠、氯和镁水平低于参考值，血钾出现危急值。SLC12A3基因检出母源致病性c.602-16G>A和父源c.805_806insTTGGCGTGGTCTCGGTCA(p.V268_T 269insIGVVSV)复合杂合变异。根据美国医学遗传学与基因组学学会指南，患者2携带的变异均被判定为致病性变异(PVS1＋PM2_Supporting＋PP3；PVS1＋PM2_Supporting＋PM4)。 结论 上述SLC12A3变异考虑为2例GS患者的遗传学病因。 Objective To explore the genetic etiology of two patients with Gitelman syndrome (GS). Methods Two patients who had presented at the Linyi People′s Hospital in January and June 2022 respectively were selected as the study subjects. Peripheral blood samples of them were collected and subjected to whole exome sequencing (WES). Electrolyte levels in their serum and urine were detected. Candidate variants were verified by Sanger sequencing. PyMOL software was used to predict the impact of the variants on the protein structure. Results Patient 1 was a 27-year-old female with decreased serum levels of sodium, potassium, chloride and magnesium, along with decreased urine chloride and calcium. WES revealed that she has harbored compound heterozygous variants of the SLC12A3 gene, namely c. 1456G>A (p.D486N) and c. 179C>T (p.T60M). The former was inherited from her mother and known to be pathogenic. Patient 2 was a 4-year-old male with lower serum sodium, chloride and magnesium levels, and his serum potassium level was found to be critically low. He was found to harbor compound heterozygous variants of c. 602-16G>A and c. 805_806insTTGGCGTGGTCTCGGTCA (p.V268_T269insIGVVSV) of theSLC12A3 gene, which were inherited from his mother and father, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+ PM2_Supporting+ PP3 PVS1+ PM2_Supporting+ PM4). Conclusion The above heterozygous variants of the SLC12A3 gene probably underlay the GS in these patients.

    肾小管Gitelman综合征SLC12A3基因基因变异

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    TBR1基因变异致全面发育落后伴自闭症1例患儿的分析

    刘金凤张佳沈亚君李杨...
    335-338页
    查看更多>>摘要：目的 分析1例全面发育落后伴自闭症患儿的临床特征及遗传学病因。 方法 选择2021年4月13日就诊于四川大学华西第二医院的1例患儿作为研究对象，回顾性分析其临床表现、实验室检查结果，并对其进行全外显子组测序(WES)，对候选变异进行致病性分析。 结果 患儿主要表现为认知、语言、运动发育落后、自闭症、癫痫发作等；脑电图显示醒睡期多灶性放电，以睡眠期为甚。头颅MRI显示巨脑回畸形、局部皮质增厚。WES显示患儿具有TBR1基因c.1589_1595dup(p.Gly533Leufs*143)杂合移码变异。根据美国医学遗传学与基因组学学会(ACMG)相关指南，判定为致病性变异(PS2＋PVS1_Supporting＋PM2_Supporting)。给予左乙拉西坦抗癫痫治疗及康复训练后，患儿近5个月未发作，运动发育较前好转。 结论 TBR1基因c.1589_1595dup变异可能为患儿的致病原因。 Objective To explore the clinical characteristics and genetic basis for a child with global developmental delay and autism. Methods A child who had presented at West China Second University Hospital of Sichuan University on April 13, 2021 was selected as the study subject. Clinical manifestations, laboratory examination and result of genetic testing were analyzed. Results The main symptoms of the child had included cognitive, language and motor delay, autism and epilepsy. Electroencephalogram revealed multiple focal discharges in both waking and sleeping stages, with the remarkable one seen at the sleeping stage. Cranial MRI showed pachygyria and local cortical thickening, Whole exome sequencing (WES) revealed that the child has harbored a heterozygous c. 1589_1595dup (p.Gly533Leufs*143) frameshifting variant in the TBR1 gene (OMIM 604616). Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be likely pathogenic (PS2+ PVS1_Supporting+ PM2_Supporting). After treated with levetiracetam and rehabilitation training, the child did not have seizure in the past 5 months, and his motor development has also significantly improved. Conclusion The c. 1589_1595dup variant of the TBR1 gene probably underlay the disease in this patient.

    基因检测全面发育落后自闭症TBR1基因全外显子组测序

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    MYO5B基因变异致微绒毛包涵体病患儿1例的遗传学分析并文献复习

    夏俊珂张心愿柳慧孔祥东...
    339-344页
    查看更多>>摘要：目的 探讨1例微绒毛包涵体病(MVID)患儿的临床特点和遗传学病因。 方法 以2019年5月至郑州大学第一附属医院就诊的1例MVID患儿为研究对象。回顾性分析其临床资料，应用全外显子组测序(WES)进行基因检测，对候选变异进行Sanger测序验证和多重连接依赖性探针扩增(MLPA)。复习文献总结MVID的临床和遗传学特点。 结果 患儿为早产男婴，表现为不明原因难治性腹泻伴酸中毒，积极对症治疗，效差，于2月龄死亡。WES发现患儿携带MYO5B基因c.1591C>T(p.R531W)杂合变异，并提示第9外显子杂合缺失。Sanger测序验证R531W变异遗传自父亲，MLPA证实第9外显子杂合缺失遗传自母亲，且为新发现的变异。国内报道7例MVID患儿中，1例失访，6例死亡；国外报道188例患者中，仅1例治愈。 结论 该MVID患儿表现为难治性腹泻伴酸中毒，预后不良。MYO5B基因R531W和第9外显子缺失复合杂合变异可能为该患儿的致病原因，为家系遗传咨询和产前诊断提供依据。 Objective To explore the clinical and genetic characteristics of a neonate with Microvillus inclusion disease (MVID). Methods A neonate with MVID admitted to the First Affiliated Hospital of Zhengzhou University in May 2019 was selected as the study subject. Clinical data were collected. Whole exome sequencing (WES) was carried out, and candidate variants were verified by Sanger sequencing and multiple ligation-dependent probe amplification (MLPA). A literature was also carried out to summarize the clinical and genetic characteristics of MVID. Results The prematurely born neonate had presented with unexplained refractory diarrhea and metabolic acidosis. Active symptomatic treatment was ineffective, and the child had died at 2 months old. WES revealed that he had harbored compound heterozygous variants of the MYO5B gene, namely c. 1591C>T (p.R531W) and deletion of exon 9. Sanger sequencing showed that the R531W variant was inherited form his father, and MLPA confirmed that the exon 9 deletion was inherited from his mother. Seven children with MVID were reported in China, of which one was lost during follow-up and six had deceased. One hundred eighty eight patients were reported worldwide and only one was cured. The clinical features of MVID had included refractory diarrhea, metabolic acidosis and poor prognosis. Conclusion The child was diagnosed with MVID due to the compound heterozygous variants of the MYO5B gene, which has provided a basis for genetic counseling and prenatal diagnosis.

    基因检测MYO5B基因微绒毛包涵体病腹泻全外显子组测序多重连接依赖性探针扩增

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    ATP6V0A1基因变异致发育性癫痫性脑病104型1例患儿的临床表型及遗传学分析

    李承燕王优陈思齐荣诗雯...
    345-350页
    查看更多>>摘要：目的 探讨1例癫痫性脑病(DEE)患儿的临床表型及遗传学病因。 方法 收集2021年2月就诊于广东医科大学附属医院儿童医学中心的1例患儿的临床资料进行回顾性分析。采集患儿及其父母的外周血样，对其进行全外显子组测序，对候选变异进行Sanger测序验证。以"ATP6V0A1基因""发育性及癫痫性脑病104型""ATP6V0A1 variant""developmental and epileptic encephalopathy 104""DEE 104""epileptic encephalopathy"为关键词检索中国知网、万方数据平台以及PubMed数据库中的相关文献，检索时间为建库至2022年12月。 结果 患儿为5月龄男性，婴儿期起病，表现为频繁的局灶性发作，伴严重发育落后，体型消瘦、小头畸形、外眦上斜，精灵耳，四肢肌张力低下。患儿脑电图提示多灶性尖波、慢波、棘慢波发放，头颅MRI发现双侧侧脑室、第三脑室扩大，脑沟、脑裂、脑池增宽。测序结果提示患儿ATP6V0A1基因存在c.2401C>T(p.His801Tyr)新发错义变异，判读为可能致病性(PS2＋PM2_Supporting＋PP3)。结合患儿的临床表型和基因检测结果，确诊其为DEE104型。共检索到ATP6V0A1基因变异所致DEE104型文献2篇，共14例。DEE104型患者变异以杂合变异为主，热点变异为c.2219G>A(10/14, 71.4%)，最常见的临床特征为难治性癫痫发作及发育迟缓(14/14, 100.0%)。 结论 患儿考虑为ATP6V0A1基因c.2401C>T的杂合变异所致的癫痫型脑病104型。 Objective To explore the clinical phenotype and genetic etiology of a child with Developmental epileptic encephalopathy type 104 (DEE 104). Methods A child who had presented at the Children′s Medical Center of the Affiliated Hospital of Guangdong Medical University in February 2021 for recurrent seizures over 1 month 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 subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. Results The child, a five-month-old male, had presented with frequent focal seizures with severe developmental retardation from infancy. Physical examination showed emaciation, microcephaly, oblique palpebral fissures, Stahl′s ears, and hypotonia in the limbs. Electroencephalogram revealed multi-focal sharp waves, slow waves and slow spinal waves. Cranial magnetic resonance imaging revealed enlargement of bilateral lateral ventricles and the third ventricle, along with widening of brain sulci, fissure and cisterna. WES revealed that he had harbored a heterozygous c. 2401C>T (p.His801Tyr) missense variant of theATP6V0A1 gene. Sanger sequencing showed that both of his parents were of the wild type. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PS2+ PM2_Supporting+ PP3). The proband was diagnosed with DEE 104. Early treatment with sodium valproate has failed, but the child had become seizure free after the addition of levetiracetam and topiramate. He still had abnormal EEG discharges and severe psychomotor retardation. Combining our case and a review of literature, DEE104 is mainly caused by de novo heterozygous variants of the ATP6V0A1 gene with an autosomal dominant inheritance. The patients may show refractory epilepsy and severe global developmental delay from infancy. Conclusion The c. 2401C>T (p.His801Tyr) variant probably underlay the DEE104 in this child.

    神经发育障碍ATP6V0A1基因发育性癫痫性脑病104型小头畸形儿童

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    单纯性少毛症1例患儿的遗传学分析

    翟玉娟李晓荟王玮窦进法...
    351-355页
    查看更多>>摘要：目的 探究1例少毛症14型患儿的临床表型与遗传学特征。 方法 选取2020年5月4日因"头发稀疏"就诊于河南省人民医院皮肤科的1例患儿作为研究对象，回顾性分析其临床资料。采集患儿及其父母的外周血样，提取基因组DNA，通过全外显子组测序筛选潜在的致病变异，并对其进行Sanger测序验证和生物信息学分析。 结果 患儿为5岁女性，头发稀疏细软，呈胎毛状，容易脱落。基因测序结果提示其LSS基因存在父源c.1609G>A(p.V537M)和母源c.802T>G(p.F268V)复合杂合变异，二者所对应的氨基酸序列在进化上高度保守。但根据美国医学遗传学与基因组学学会(ACMG)相关指南，二者均被均评级为意义不明(PM2_Supporting＋PP3＋PP4)。 结论 LSS基因c.1609G>A(p.V537M)和c.802T>G(p.F268V)杂合变异可能是患儿存在头发稀疏细软的遗传学病因。 Objective To explore the clinical phenotype and genetic characteristics of a child with Hypotrichosis 14. Methods A child who had presented at the Henan Provincial People′s Hospital on May 4, 2020 due to hair thinning was selected as the study subject. Clinical data of the child was collected. Peripheral venous blood samples were collected from the child and her parents. Genomic DNA was extracted and subjected to whole exome sequencing. Candidate variants were validated by Sanger sequencing and bioinformatic analysis. Results The child, a 5-year-old female, had presented with thin, soft lanugo-like hair which was easy to fall off. The child was found to harbor compound heterozygous missense variants of the LSS gene, namely c. 1609G>A (p.V537M) in exon 17 and c. 802T>G (p.F268V) in exon 8, which were respectively inherited from her father and mother. Both variant sites were highly conserved, though based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as variants of unknown significance (PM2_Supporting+ PP3+ PP4). Conclusion The c. 1609G>A (p.V537M) and c. 802T>G (p.F268V) compound heterozygous variants of theLSS gene probably underlay the clinical phenotype in this patient.

    基因检测少毛症14型基因变异LSS基因

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    KMT2D基因变异相关歌舞伎综合征1例的遗传学分析

    黄娟李秋雨吉炜郭晓峰...
    356-362页
    查看更多>>摘要：目的 探讨1例KMT2D基因变异的歌舞伎综合征(KS)患儿的遗传学特征。 方法 选取2022年7月25日于福建省儿童医院就诊的1例KS患儿作为研究对象进行回顾性研究。对患儿及其父母进行全外显子组测序，并应用Sanger测序对候选变异进行验证，通过相关数据库及软件对其进行致病性分析。 结果 患儿为4月龄女性，临床特征包括特殊面容、生长发育迟缓、心脏畸形、马蹄肾、甲状腺功能减退以及反复吸入性肺炎。全外显子组测序显示该患儿存在KMT2D基因c.6285dup(p.Lys2096Ter)杂合变异，Sanger测序验证其父母均未携带该变异，提示其为新发变异。该变异位点具有高度保守性，蛋白功能分析提示蛋白截短，酶促活性区域丢失。根据美国医学遗传学与基因组学学会(ACMG)相关指南，该变异被评定为致病性变异(PVS1＋PS2＋PM2_Supporting)。 结论 KMT2D基因c.6285dup变异可考虑为患儿患KS的致病原因。 Objective To report on a case of Kabuki syndrome (KS) due to a novel variant of KMT2D gene. Methods A child diagnosed with KS at the Fujian Children′s Hospital on July 25, 2022 was selected as the study subject. Whole exome sequencing was carried out for the child and her parents. Candidate variant was validated by Sanger sequencing and bioinformatic analysis. Results The child, a 4-month-old female, had presented with distinctive facial features, growth retardation, cardiac malformations, horseshoe kidney, hypothyroidism, and recurrent aspiration pneumonia. Whole exome sequencing revealed that she has harbored a heterozygous c. 6285dup (p.Lys2096Ter) variant of the KMT2D gene. Sanger sequencing confirmed that neither of her parents had carried the same variant. The variant was previously unreported, and may result in a truncated protein and loss of an enzymatic activity region. The corresponding site of the variant is highly conserved. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PVS1+ PS2+ PM2_Supporting). Conclusion The c. 6285 dup variant of the KMT2D gene probably underlay the KS in this child.

    发育障碍歌舞伎综合征KMT2D基因基因变异

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