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

    外周血胎儿游离DNA产前筛查高风险者的产前诊断及妊娠结局分析

    李照侠段红蕾刘威朱瑞芳...
    1-7页
    查看更多>>摘要：目的 分析747例孕妇外周血胎儿游离DNA产前筛查高风险胎儿产前诊断结果及妊娠结局。 方法 选取2015年1月至2022年3月在南京鼓楼医院因孕妇外周血胎儿游离DNA无创产前筛查(NIPT)高风险行羊膜腔穿刺产前诊断的747例病例，均行羊水细胞染色体核型分析和/或染色体微阵列分析。对所有病例进行查阅分娩资料或电话等形式的随访并记录结果。组间采用χ2检验或者F检验进行统计学处理。 结果 747例NIPT高风险孕妇中387例为真阳性，整体阳性预测值(PPV)为51.81%。NIPT对21三体(T21)、18三体(T18)、13三体(T13)、性染色体非整倍体(SCA)高风险的PPV分别为80.24%(199/248)、60%(48/80)、14%(7/50)、38.97%(106/272)，对T21的PPV显著高于T18和T13(P<0.001)。NIPT对其他染色体非整倍体高风险和染色体拷贝数变异(CNV)的PPV分别为11.11%(5/45)和40.74%(22/52)。对X染色体增加的PPV明显高于X染色体减少(64.29%vs. 22.22%，P<0.05)。高龄(≥35岁)孕妇总体PPV显著高于低龄组(69.35%vs. 42.39%，P<0.001)。T21、T18的Z≥10组PPV明显高于3≤Z<5组和5≤Z<10组(P<0.05)。52例CNV高风险中，≤5 Mb的PPV显著高于5 Mb<CNV≤10 Mb和>10 Mb(60%vs. 30%；60% vs. 23.53%，P<0.05)。387例真阳性病例中，322例引产，53例分娩且生长发育未见异常，12例失访。 结论 NIPT对常见非整倍体异常的PPV与孕妇年龄及Z值相关，高龄人群、高Z值组的阳性预测值较高。 Objective To analyze the results of prenatal diagnosis and outcome of pregnancy for women with a high risk for fetal aneuploidies. Methods A total of 747 cases of prenatal diagnosis by amniocentesis due to high risks by non-invasive prenatal testing (NIPT) were selected from January 2015 to March 2022 in the Drum Tower Hospital Affiliated to Nanjing University Medical School. The amniotic fluid samples were subjected to chromosomal karyotyping and/or chromosomal microarray analysis. All cases were followed up by searching the birth information or telephone calls, and the results were recorded. 2 test or F test were used for comparing the difference between the groups. Results Among the 747 pregnant women with a high risk by NIPT, 387 were true positives, and the overall positive predictive value (PPV) was 51.81%. The PPVs for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13) and sex chromosome aneuploidies (SCA) were 80.24% (199/248), 60% (48/80), 14% (7/50) and 38.97% (106/272), respectively. The PPV for T21 was significantly higher than T18 and T13 (χ2= 85.216, P<0.0001). The PPV for other chromosomal aneuploidies and copy number variations (CNVs) were 11.11% (5/45) and 40.74% (22/52), respectively. The PPV for increased X chromosomes was significantly higher than X chromosome decreases (64.29%vs. 22.22%, χ2= 5.530, P<0.05). The overall PPV for elder women (≥ 35 years old) was significantly higher than younger women (69.35%vs. 42.39%, χ2= 49.440, P<0.0001). For T21 and T18, the PPV ofZ ≥ 10 group was significantly higher than that for 3 ≤ Z < 5 group or 5 ≤ Z < 10 group ( P<0.05). Among 52 cases with a high risk for CNVs, the PPV for the ≤ 5 Mb group was significantly higher than the 5 Mb < CNVs < 10 Mb or > 10 Mb groups (60%vs. 30%和60% vs. 23.53%, P<0.05). Among the 387 true positive cases, 322 had opted for induced labor, 53 had delivered with no abnormal growth and development, and 12 were lost during the follow-up. Conclusion The PPVs for common chromosomal aneuploidies are related to the age and Z value of the pregnant women, which were higher in the elder group and higher Z value group. In addition, the PPV is associated with high risk types. The PPV for T21 was higher than T18 and T13, and that for 45, X was lower than 47, XXX, 47, XYY or 47, XXY syndrome. NIPT therefore has relatively high PPVs for the identification of chromosomal CNVs.

    产前诊断外周血胎儿游离DNA拷贝数变异妊娠结局阳性预测值核型分析染色体微阵列分析

      原文链接:
    • 万方数据

    NIPT-PLUS检测7-三体假阳性合并18-三体假阴性的遗传学分析

    肖艳华王爱玲李瑞王建红...
    8-13页
    查看更多>>摘要：目的 探讨1例扩展性无创产前检测(NIPT-PLUS)提示7-三体和产前诊断提示18-三体结果不一致的原因。 方法 选取2020年7月5日于焦作市妇幼保健院进行遗传咨询的1例孕妇为研究对象。对孕妇进行NIPT-PLUS检测、系统超声检查及介入性产前诊断。引产后分别取脐带中间段、母亲面胎盘中心、母亲面胎盘边缘、胎儿面脐带根部、胎儿面胎盘边缘及胎儿面胎盘中心6个位置组织，行拷贝数变异测序(CNV-seq)检测进行验证。 结果 NIPT-PLUS结果提示胎儿为7-三体，系统超声提示胎儿房室间隔缺损、马蹄肾、摇椅足等多发畸形，羊水QF-PCR、核型分析和CNV-seq结果均提示胎儿为18-三体，证实胎儿为NIPT-PLUS检测7-三体假阳性合并18-三体假阴性。引产后胎盘验证结果显示脐带中间段为18-三体，胎儿面胎盘中心为7-三体，胎盘其他位置均呈现7-三体和18-三体嵌合现象，且距离脐带越远，18-三体嵌合比例越低。 结论 本研究NIPT-PLUS检测7-三体假阳性合并18-三体假阴性由胎盘嵌合所致。当NIPT-PLUS检测提示非整倍体时，需进行严格产前诊断以排除胎盘嵌合对误诊的影响。 Objective To explore the cause of inconsistency between the results of trisomy 7 by expanded non-invasive prenatal testing (NIPT-PLUS) and trisomy 18 by prenatal diagnosis. Methods A pregnant woman who received genetic counseling at Jiaozuo Maternal and Child Health Care Hospital on July 5, 2020 was selected as the study subject. NIPT-PLUS, systematic ultrasound and interventional prenatal testing were carried out. The middle segment and root of umbilical cord, center and edge of the maternal and fatal surface of the placenta were sampled for the validation by copy number variation sequencing (CNV-seq). Results The result of NIPT-PLUS indicated that the fetus has trisomy 7. Systematic ultrasound has shown multiple malformations including atrioventricular septal defect, horseshoe kidney, and rocker-bottom feet. However, QF-PCR, chromosomal karyotyping analysis, and CNV-seq of amniotic fluid samples all showed that the fetus was trisomy 18. Validation using multiple placental samples confirmed that the middle segment of the umbilical cord contains trisomy 18, the center of the placenta contained trisomy 7, and other placental sites were mosaicism for trisomy 7 and trisomy 18. Notably, the ratio of trisomy 18 became lower further away from the umbilical cord. Conclusion The false positive results of trisomy 7 and false negative trisomy 18 by NIPT-PLUS was probably due to the existence of placental mosaicism. Strict prenatal diagnosis is required needed aneuploidy is detected by NIPT-PLUS to exclude the influence of placental mosaicisms.

    7-三体18-三体假阳性假阴性系统超声胎盘嵌合

      原文链接:
    • 万方数据

    无创产前检测在双胎妊娠中的临床应用

    王晶汪雪雁宋筱左萍...
    14-19页
    查看更多>>摘要：目的 评估无创产前检测(NIPT)筛查双胎妊娠染色体非整倍体异常的可行性。 方法 收集双胎妊娠的孕妇外周血样2 745份，用NIPT进行检测，对高风险的孕妇进行羊水穿刺染色体核型以及染色体微阵列分析检测，随访产前诊断的结果以及妊娠结局，计算NIPT对双胎妊娠染色体非整倍体异常检测的灵敏度、特异度、阳性预测值和假阳性率。 结果 与其他染色体异常相比，NIPT对双胎妊娠中的21三体以及性染色体非整倍体异常检出率更高(敏感性均为100%，特异性分别为99.93%和99.9%)，对于18三体以及13三体，因数据有限难以评估其筛查效能。对于15 ～ 21 Mb的染色体微重复或微缺失，NIPT也有一定的检出率。相比自然受孕的双胎孕妇，NIPT在辅助生殖的双胎孕妇中具有更高的阳性检出率(P<0.05)。 结论 采用NIPT对双胎进行染色体非整倍体异常的筛查是可行的。 Objective To evaluate the feasibility of non-invasive prenatal testing (NIPT) for the screening of fetal chromosome aneuploidies in twin pregnancies. Methods A total of 2 745 women with twin-pregnancies were subjected for NIPT screening. Chromosomal karyotyping and chromosomal microarray analysis (CMA) were carried out on amniotic fluid samples from those with a high risk for fetal chromosome aneuploidies, and the diagnosis and pregnancy outcome were followed up. The sensitivity, specificity, positive predictive value and false positive rate of the NIPT were calculated. Results Compared with other chromosomal abnormalities, NIPT had a higher efficacy for trisomy 21 and sex chromosomal aneuploidy (SCA) in twin pregnancies (with sensitivity being 100%, 100%, and specificity being 99.93%, 99.9%, respectively). It is difficult to evaluate the efficacy for trisomies 18 and 13 due to the limited data. For chromosome microdeletions and microduplications spanning 15 ~ 21 Mb, NIPT also had a certain detection rate. Compared with women with natural conception, NIPT had a higher detection rate for those with twin pregnancies by assisted reproduction (P < 0.05). Conclusion It is feasible to use NIPT for the detection of chromosome aneuploidies in women with twin pregnancies.

    无创双胎染色体非整倍体异常21三体性染色体非整倍体

      原文链接:
    • 万方数据

    数字PCR技术检测脊髓性肌萎缩症携带者的应用评估

    闫有圣陈芊如张萌王芳...
    20-24页
    查看更多>>摘要：目的 应用数字PCR方法进行脊髓性肌萎缩症(SMA)携带者检测，评价其效果以及将其用于SMA携带者筛查的可行性。 方法 收集常规进行产前SMA携带者筛查的孕妇外周血样本214例，其中204例为随机样本，10例为已知SMN1第7和第8外显子拷贝数的样本，随机掺入实验中，用于对数字PCR方法进行性能验证。采用数字PCR方法对外周血DNA样本中SMN1和SMN2基因的第7和第8外显子拷贝数进行检测，并与荧光定量PCR的检测结果进行比较，评估数字PCR方法的可靠性和检测效能。 结果 采用数字PCR方法在204例随机样本中检测到SMN1第7和第8外显子同时杂合缺失样本5例，仅SMN1第8外显子杂合缺失样本3例，SMN1第7和第8外显子未缺失样本196例。10例已知SMN1第7和第8外显子拷贝数样本的检测结果与预期值一致。通过与荧光定量PCR检测结果比较，数字PCR对于SMN1第7和第8外显子拷贝数的检测结果的一致率为100%。 结论 数字PCR检测SMN1第7和第8外显子的缺失情况结果与qPCR一致，并且能够明确区分目标基因的拷贝数，该方法可用于SMA致病基因的携带者筛查。此外，数字PCR还能检测SMN2第7和第8外显子的拷贝数，提供更多的信息。 Objective To assess the effectiveness and feasibility of carrier detection for Spinal muscular atrophy (SMA) by using digital PCR assay. Methods Peripheral blood samples were collected from 214 pregnant women who were routinely screened for SMA carriers, of which 204 were randomly selected samples and 10 were samples with known copy numbers of SMN1 exons 7 and 8. Samples with known copy numbers of SMN1 exons 7 and 8 were randomly mixed into the experiment to validate the performance of the digital PCR assay. The copy numbers of SMN1 exons 7 and 8 and SMN2 exons 7 and 8 in peripheral blood samples were detected by digital PCR assay. The results of SMN1 exons 7 and 8 were compared with those of the quantitative PCR method to assess the reliability and clinical performance of the digital PCR assay. Results Among the 204 random samples, digital PCR has detected five samples with simultaneous heterozygous deletion of SMN1 exons 7 and 8, three samples with heterozygous deletion of SMN1 exon 8 only, and 196 samples with no deletion of SMN1 exons 7 and 8. Ten samples with known SMN1 exons 7 and 8 copy numbers were detected with the expected values. The digital PCR test results were fully consistent with that of the quantitative PCR. Conclusion The results of digital PCR for the detection of copy number variation of SMN1 exons 7 and 8 were consistent with qPCR. Digital PCR assay was able to clearly distinguish the copy number of the target genes, therefore can be used for SMA carrier screening. Moreover, it can also detect copy number of SMN2 exons 7 and 8, which can provide more information for genetic counseling.

    脊髓性肌萎缩症荧光定量PCR数字PCR携带者筛查

      原文链接:
    • 万方数据

    SYNGAP1基因变异患儿的早期神经发育表型与基因型的相关性

    刘浩然杨圣海李佳一谢华...
    25-31页
    查看更多>>摘要：目的 探讨SYNGAP1基因变异患儿的早期智力发育障碍表型，并确定其基因型与表型的相关性。 方法 将2019年1月至2022年7月就诊于首都儿科研究所附属儿童医院、通过全外显子组测序检出SYNGAP1基因变异的幼儿(< 5岁)作为研究对象。所有患儿均完成了儿童神经心理发育评估、家系验证和基因变异的致病性评估。在文献中检索携带SYNGAP1基因致病/可能致病变异的小年龄段幼儿(< 5岁)，必须有详细表型、0 ～ 6岁神经心理发育量表或其他神经心理发育状态评估数值，作为SYNGAP1基因变异患儿的早期神经发育表型特点，之后分析其表型特点与基因型的相关性。 结果 共纳入4例携带SYNGAP1基因可能致病/致病变异的患儿(1男3女，平均年龄为34.0 ± 18.2个月)，其中1例携带既往未见报道的变异(c.437C>G，p.S146*)。文献检索共发现19例患儿。在23例携带SYNGAP1基因变异的患儿(8男10女，5名性别未知，年龄为37.1 ± 14.2个月)中，19例(82.6%)为功能丧失变异。所有患儿均在2岁前出现全面发育迟缓，有16例(69.6%)出现惊厥/癫痫发作，发病年龄为27.0 ± 12.1个月，其中15例的惊厥/癫痫出现在发育迟缓之后，提示早期全面发育迟缓并非惊厥/癫痫引起。肌阵挛发作和失神发作是其常见的发作类型。与携带第8 ～ 15外显子变异者相比，第1 ～ 5外显子变异者发育迟缓严重程度较轻。 结论 携带SYNGAP1基因变异的小年龄患者主要表现为全面发育迟缓和癫痫，在2岁前即出现发育迟缓，其严重程度可能与变异类型和所在的外显子有关。 Objective To explore the early neurodevelopmental features of young children with SYNGAP1 variants and their genotype-phenotype correlation. Methods Young children with neurodevelopmental disorders (NDDs) (< 5 years old) who were referred to the Children′s Hospital Affiliated to the Capital Institute of Pediatrics between January 2019 and July 2022 were selected as the study subjects. All children had undergone whole-exome sequencing, comprehensive pediatric neuropsychological assessment, familial segregation analysis, and pathogenicity classification. Meanwhile, young Chinese NDD children (< 5 years old) with pathogenic/likely pathogenicSYNGAP1 variants were retrieved from the literature, with information including detailed clinical and genetic testing, neurodevelopmental quotient (DQ) of the Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016). Children who did not have a detailed DQ but had their developmental status assessed by a medical professional were also included. The correlation between neurodevelopmental severity, comorbidity and SYNGAP1 variants were summarized. Results Four young NDD children carrying SYNGAP1 variants were recruited (1 male and 3 females, with a mean age of 34.0 ± 18.2 months), among whom one harboring a novel variant (c.437C>G, p. S146*). Combined with 19 similar cases retrieved from the literature, 23 Chinese NDD young children were included in our study (8 males and 10 females, 5 with unknown sex, with a mean age of 37.1 ± 14.2 months). A loss of function (LOF) variant was found in 19 (82.6%) children. All of the children had presented global developmental delay (GDD) before the age of two. In addition, 16 (69.6%) had seizure/epilepsy at the age of 27.0 ± 12.1 months, among whom 15 had occurred independent of the global developmental delay. Myoclonic and absence were common types of seizures. Compared with those with variants of exons 8 to 15, the severity of developmental delay was milder among children with variants in exons 1 to 5. Conclusion The early neurodevelopment features of the SYNGAP1 variants for young children (< 5 years old) have included global developmental delay and seizure/epilepsy. All of the children may present GDD before the age of two. The severity of developmental delay may be related to the type and location of theSYNGAP1 variants.

    SYNGAP1变异全面发育迟缓惊厥/癫痫<5岁

      原文链接:
    • 万方数据

    西南地区人群 PHOX2B基因GCN重复变异的调查以及2例先天性中枢性低通气综合征患儿的诊断

    秦胜芳叶梦玲尹雁王锦...
    32-37页
    查看更多>>摘要：目的 调查西南地区健康人群PHOX2B基因第3外显子编码丙氨酸的GCN(GCA、GCT、GCC、GCG)三碱基重复数的分布，并对2例先天性中枢性低通气综合征(CCHS)患儿的GCN重复数进行分析。 方法 分别采用毛细管电泳分析、Sanger测序、克隆测序分析518例健康个体和2例CCHS患儿及其父母PHOX2B基因的GCN重复数和碱基序列。 结果 对518例健康个体的1036个等位基因进行分析，共发现5种等位基因，其中以(GCN)20频率最高，达94.79%；共发现5种基因型，其中(GCN)20/(GCN)20纯合子占89.58%。(GCN)20纯合基因型由4种不同的GCN重复碱基序列组成。PHOX2B基因GCN重复的基因型在调查人群中达到了遗传平衡。两例CCHS患儿的基因型分别为(GCN)20/(GCN)25和(GCN)20/(GCN)30。 结论 调查正常人群中PHOX2B的GCN重复数分布和基因型数据具有重要的意义。518例健康个体的GCN重复数均在20以下。准确检出PHOX2B基因的重复扩增突变将有助于CCHS的早期诊断和治疗。 Objective To study the trinucleotide repeats of GCN (GCA, GCT, GCC, GCG) encoding Alanine in exon 3 of the PHOX2B gene among healthy individuals from southwest China and two patients with Congenital central hypoventilation syndrome (CCHS). Methods The number and sequence of the GCN repeats of the PHOX2B gene were analyzed by capillary electrophoresis, Sanger sequencing and cloning sequencing of 518 healthy individuals and two newborns with CCHS, respectively. Results Among the 1036 alleles of the 518 healthy individuals, five alleles were identified, including (GCN)7, (GCN)13, (GCN)14, (GCN)15 and (GCN)20. The frequency of the (GCN)20 allele was the highest (94.79%). And five genotypes were identified, which included (GCN)7/(GCN)20, (GCN)13/(GCN)20, (GCN)14/(GCN)20, (GCN)15/(GCN)20, (GCN)20/(GCN)20. The homozygous genotypes were all (GCN)20/(GCN)20, and the carrier rate was 89.58%. Four GCN sequences of the (GCN)20 homozygous genotypes were identified among the 464 healthy individuals. The GCN repeat numbers in the exon 3 of the PHOX2B gene showed no significant difference between the expected and observed values, and had fulfilled the, Hardy-Weinberg equilibrium. The genotypes of the two CCHS patients were (GCN)20/(GCN)25 and (GCN)20/(GCN)30, respectively. Conclusion It is important to determine the GCN repeats and genotypic data of the exon 3 of the PHOX2B gene among the healthy individuals. The number of GCN repeats in 518 healthy individuals was all below 20. The selection of appropriate methods can accurately detect the polyalanine repeat mutations (PARMs) of the PHOX2B gene, which is conducive to the early diagnosis, intervention and treatment of CCHS.

    PHOX2B基因GCN重复基因测序毛细管电泳先天性中枢性低通气综合征

      原文链接:
    • 万方数据

    WNT1基因突变所致成骨不全症患者皮肤组织来源诱导多能干细胞系的建立

    杜松杰管鑫张美丽赵秀丽...
    38-41页
    查看更多>>摘要：目的 建立WNT1基因突变(WNT1c.677C>T)所致成骨不全症患者皮肤组织来源的诱导多能干细胞(induced pluripotent stem cells，iPSCs)系，为疾病相关的分子机制研究和干细胞治疗提供新的细胞模型。 方法 通过Sanger测序明确患者的致病变异。在征得患者知情同意后，采集其皮肤组织样本，原代培养皮肤成纤维细胞。利用仙台病毒介导的非基因组整合的体细胞重编程方法，将皮肤成纤维细胞诱导为iPSCs，并对其进行多能性、分化能力以及核型鉴定。 结果 患者携带WNT1基因c.677C>T(p.Ser226Leu)纯合错义突变。由其皮肤成纤维细胞重编程建立的iPSCs系具备自我更新及体外分化能力，核型为正常的二倍体(46，XX)。 结论 建立了患者来源的WNT1基因突变(WNT1c.677C>T)iPSCs系，为该突变所致成骨不全症的研究提供了新的细胞模型。 Objective To obtain skin-derived induced pluripotent stem cells (iPSCs) from an Osteogenesis imperfecta (OI) patient carrying WNT1c.677C>T mutation in order to provide a new cell model for investigating the underlying molecular mechanism and stem cell therapy for OI. Methods The pathogenic variant of the patient was identified by Sanger sequencing. With informed consent from the patient, skin tissue was biopsied, and primary skin fibroblasts were cultured. Skin fibroblasts were induced into iPSCs using Sendai virus-mediated non-genomic integration reprogramming method. The iPSC cell lines were characterized for pluripotency, differentiation capacity, and karyotyping assay. Results The patient was found to carry homozygous missense c. 677C>T (p.Ser226Leu) mutation of theWNT1 gene. The established iPSC lines possessed self-renewal and capacity for in vitro differentiation. It also has a diploid karyotype (46, XX). Conclusion A patient-specific WNT1 gene mutation (WNT1c.677C>T) iPSC line was established, which can provide a cell model for the study of OI caused by the mutation.

    成骨不全症WNT1c．677C>T突变诱导多能干细胞仙台病毒

      原文链接:
    • 万方数据

    中国汉族人群 D13S317基因座的多态性及新的三带型等位基因序列的遗传学研究

    高素青何柳媚李桢张胤鸣...
    42-46页
    查看更多>>摘要：目的 分析中国汉族人群短串联重复序列(STR)D13S317基因座等位基因多态性，发现及鉴定中国人群中D13S317基因座新的STR三带型等位基因，排除非特异性扩增及侧翼序列基因变异产生的三带型等位基因，研究新的三带型等位基因序列特征及遗传方式。 方法 选取2017年10月17日至2018年12月28日于广东深光法医物证司法鉴定所进行鉴定的378例样本为研究对象。常规采用GlobalFiler™ Express试剂盒作STR基因分型初检，对疑似三带型等位基因的家系采用PowerPlex® 21试剂盒作STR基因分型复检，复检后采用分子克隆测序技术排除引物结合区及侧翼序列基因变异产生的三带型等位基因的可能。 结果 初检共计检出6个D13S317等位基因，基因频率分布特征分别是8(29.1%)、9(13.1%)、10(15.21%)、11(24.21%)、12(13.89%)和13(3.44%)；其中有1个家系中先证者的D13S317基因座疑似为三带型等位基因(8、9、10)。复检与初检结果一致。先证者及其女儿D13S317基因座分子克隆测序分析未发现引物结合区及侧翼序列有基因变异，确认先证者D13S317基因座为三带型等位基因。 结论 在中国人群中确认了1例D13S317基因座2型三带型等位基因(8、9、10)，该三带型等位基因未遗传给女性子一代，并首次被国际STRBase数据库收录。 Objective To study the genetic polymorphisms of short-tandem repeats (STR) for the D13S317 locus among an ethnic Han Chinese population and verify a novel tri-allelic pattern identified for the locus. Methods A total of 378 paternity test cases from Guangdong Forensic Authentication Institute from October 17, 2017 to December 28, 2017 were selected as the study subjects. A GlobalFiler™ Express kit was used for the STR genotyping. Samples suspected for having a novel tri-allelic pattern were verified with a PowerPlex® 21 kit. Potential variant of the primer-binding region and flanking sequences underlying the tri-allelic pattern was excluded by molecular cloning and sequencing. Results Six alleles were detected for the D13S317 locus, with the characteristic distribution frequencies being 8 (29.1%), 9 (13.1%), 10 (15.21%), 11 (24.21%), 12 (13.89%) and 13 (3.44%), respectively. In one of the families, the D13S317 locus of the proband was suspected to harbor a triband allele (8, 9, 10). A re-test has confirmed the result of initial test. Molecular cloning and sequencing analysis of the D13S317 locus in the proband and his daughter has failed to find allelic variants in the primer-binding region and flanking sequence, which has confirmed the novel tri-allelic pattern for the locus. Conclusion A novel type 2 tri-allelic pattern (8, 9, 10) at the D13S317 locus has been identified among the ethnic Han Chinese population. The pattern has not been transmitted to the female offspring, and has been included in the international STRBase database for the first time.

    短串联重复亲子鉴定三带型等位基因基因频率

      原文链接:
    • 万方数据

    HLA-B位点等位基因丢失一个家系的遗传学分析

    何柳媚全湛柔钟艳平邹红岩...
    47-51页
    查看更多>>摘要：目的 探讨1个家系的HLA-B基因的碱基缺失情况。 方法 选取2022年4月就诊于广西柳州市人民医院的1例急性髓系白血病女性患者、丈夫和女儿作为研究对象，应用PCR-序列特异性寡核苷酸探针(PCR-SSOP)及PCR-直接测序法(PCR-SBT)对该家系进行人类白细胞抗原(HLA)常规检测。应用二代测序技术(NGS)对HLA-B基因序列进行确认。 结果 患者及其女儿HLA-B位点的PCR-SBT和PCR-SSOP结果不一致，PCR-SSOP结果分别为HLA-B*35：01，40：02和HLA-B*35：01，40：01，PCR-SBT结果则均提示与最接近的HLA-B*35：01在第4外显子处有错配。NGS结果显示患者及其女儿HLA-B*35：01第5内含子处有1段9 bp的碱基序列缺失。患者丈夫结果为HLA-B*40：01，58：01，无异常。 结论 该家系HLA-B基因第5内含子处的变异位于SBT检测的引物结合区，影响了PCR-SBT分型结果的准确性。 Objective To delineate a deletional mutation of the HLA-B gene in a Chinese pedigree. Methods A female patient with acute myeloid leukemia who had visited Liuzhou People′s Hospital in April 2022 was selected as the study subject. Routine human leukocyte antigen (HLA) was determined by using PCR-sequence specific oligonucleotide polymorphism (PCR-SSOP) and PCR-sequence-based typing (PCR-SBT) methods. Next generation sequencing (NGS) was used to validate the candidate variant in the HLA-B gene. Results The PCR-SBT and SSOP results for the HLA-B locus were inconsistent for the patient and her daughter. The SSOP results of the two individuals were HLA-B*35: 01, 40: 02 and HLA-B*35: 01, 40: 01, respectively. However, the PCR-SBT results has indicated a mismatch with the nearest HLA-B*35: 01 at exon 4. NGS results showed that the HLA-B*35: 01 had a 9 bp deletion in the intron 5. The patient′s husband was HLA-B*40: 01, 58: 01, which was normal. Conclusion The variant in intron 5 of the HLA-B gene in this pedigree has mapped to a primer-binding region for the SBT reagent, which has affected the accuracy of PCR-SBT results.

    HLA-B基因碱基缺失PCR-序列特异性寡核苷酸探针PCR-直接测序法二代测序

      原文链接:
    • 万方数据

    Junior血型基因检测技术的建立与1例部分DVI.3型且Jr(a-)稀有血型的鉴定

    梁爽莫春妍刘笑阳姬艳丽...
    52-58页
    查看更多>>摘要：目的 建立Junior血型基因分型技术，用于Jr(a-)稀有血型的鉴定和筛查。 方法 选取2021年1月至2021年5月于深圳市血液中心无偿献血的O型RhD＋健康受试者(n＝1 568)和1个疑难交叉配血家系(n＝3)，共1 571例，为研究对象。用血清学检测技术进行先证者血型鉴定、意外抗体鉴定以及抗体效价测定。用聚合酶链反应-序列特异性引物(PCR-SSP)技术进行先证者RHD基因分型。建立ABCG2基因编码区测序和PCR-SSP基因分型技术，对先证者及其家系成员进行基因型检测，并在深圳地区无偿献血者人群(n＝1 568)中开展Jra抗原阴性的稀有血型献血者筛查。 结果 先证者ABO血型为B型，RhD血型为部分D(RHD*DVI.3/RHD*01N.01)，Junior血型Jra抗原为阴性，血浆存在抗-D合并抗-Jra。ABCG2基因测序发现先证者等位基因型为ABGG2*01N.01/ABGG2*01N.01[c.376C>T(p.Gln126X)纯合变异]，为亚洲人群中最常见的Jr(a-)血型等位基因。在深圳地区无偿献血者人群中进行筛查，无Jr(a-)稀有血型献血者检出。通过杂合子的统计分析，发现ABCG2*01N.01(c.376T)的等位基因型频率约为0.45%，这一分子背景的Jr(a-)稀有血型在深圳地区的出现频率约为0.2‰。 结论 本研究发现国内首例部分DVI.3型且Jr(a-)稀有血型，并成功建立Junior血型ABCG2基因编码区测序以及PCR-SSP基因分型技术。 Objective To develop a genotyping method for the Junior blood type and report on a rare blood type with Jr(a-). Methods Healthy O-type RhD+ volunteer donors of the Shenzhen Blood Center from January to May 2021 (n=1 568) and a pedigree with difficult cross-matching (n=3) were selected as the study subjects. Serological methods were used for proband′s blood type identification, unexpected antibody identification, and antibody titer determination. Polymerase chain reaction-sequence specific primer (PCR-SSP) method was used for typing the proband′s RHD gene. ABCG2 gene coding region sequencing and a PCR-SSP genotyping method were established for determining the genotypes of the proband and his family members and screening of Jra antigen-negative rare blood type among the 1 568 blood donors. Results The proband′s ABO and RhD blood types were respectively determined as B and partial D (RHDDVI.3/RHD01N.01), Junior blood type Jra antigen was negative, and plasma had contained anti-D and anti-Jra. Sequencing of the ABCG2 gene revealed that the proband′s genotype was ABGG201N.01/ABGG201N.01 [homozygous c. 376C>T (p.Gln126X) variants], which is the most common Jr(a-) blood type allele in the Asian population. Screening of the voluntary blood donors has detected no Jr(a-) rare blood type. Statistical analysis of the heterozygotes suggested that the allelic frequency forABCG2*01N.01 (c.376T) was 0.45%, and the frequency of Jr(a-) rare blood type with this molecular background was about 0.2‰. Conclusion A very rare case of partial DVI.3 type and Jr(a-) rare blood type has been identified. And a method for identifying the Junior blood type through sequencing the coding regions of the ABCG2 gene and PCR-SSP has been established.

    血型基因分型Jr(a-)稀有血型

      原文链接:
    • 万方数据