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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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    EAST/SeSAME综合征患儿1例的临床特征及遗传学分析

    张广宇王明梅陈功勋杨磊...
    838-841页
    查看更多>>摘要：目的 探讨1例表现为癫痫、感音神经性耳聋、共济失调、智力障碍的男性EAST/SeSAME患儿的遗传学病因。 方法 选取2021年1月至郑州大学第三附属医院就诊的1例EAST/SeSAME综合征患儿为研究对象。对患儿及其父母进行高通量测序检测，对候选变异进行Sanger测序验证及生物信息学分析。 结果 测序结果显示患儿KCNJ10基因存在c.557T>C(p.Val186Ala)和c.386T>A(p.Ile129Asn)复合杂合变异，Sanger测序证实二者分别遗传自其母亲和父亲。根据美国医学遗传学与基因组学学会(ACMG)相关指南，二者均判定为可能致病性变异(PM1+PM2_Supporting+PP3+PP4 PM1+PM2_Supporting+PM3+PP3+PP4)。 结论 患者为KCNJ10基因复合杂合变异所致的EAST/SeSAME综合征。上述发现丰富了KCNJ10基因的变异谱，并为患儿家庭的遗传咨询及产前诊断提供了依据。 Objective To explore the genetic basis for a EAST/SeSAME child featuring epilepsy, ataxia, sensorineural deafness and intellectual disability. Methods A child with EAST/SeSAME syndrome who presented the Third Affiliated Hospital of Zhengzhou University in January 2021 was selected as the study object. Peripheral blood samples of the child and her parents were collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. Results Genetic testing revealed that the child has harbored compound heterozygous variants of the KCNJ10 gene, namely c. 557T>C (p.Val186Ala) and c. 386T>A (p.Ile129Asn), which were inherited from her mother and father, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted as likely pathogenic(PM1+ PM2_Supporting+ PP3+ PP4 PM1+ PM2_Supporting+ PM3+ PP3+ PP4). Conclusion The patient was diagnosed with EAST/SeSAME syndrome due to the compound heterozygous variants of the KCNJ10 gene.

    EAST/SeSAME综合征KCNJ10基因二代测序

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    GALT基因复合杂合变异所致1例半乳糖血症患者的临床特点及遗传学分析

    谢振华刘菁李娴肖梦君...
    842-846页
    查看更多>>摘要：目的 分析1例GALT基因变异所致的半乳糖血症患儿的临床及遗传学特点。 方法 以2019年11月20日就诊于郑州大学附属儿童医院的1例患儿作为研究对象。收集其临床资料，并对其进行全外显子组测序分析，对候选变异进行Sanger测序家系验证。 结果 患儿表现为贫血、喂养困难、黄疸、肌张力低下、肝功能异常、凝血功能异常等。血氨基酸及酰基肉碱谱显示瓜氨酸、蛋氨酸、鸟氨酸、酪氨酸水平升高。尿有机酸分析显示苯乳酸、4-羟基苯乙酸、4-羟基苯乳酸、4-羟基苯丙酮酸、N-乙酰酪氨酸水平升高。基因检测显示患儿GALT基因存在c.627T>A(p.Y209*)和c.370G>C(p.G124R)复合杂合变异，分别遗传自其表型正常的父母。前者为已报道的无义变异，依据美国医学遗传学与基因组学学会(ACMG)相关指南判断为可能致病性变异；后者为未见报道的错义变异，依据ACMG相关指南判断为可能致病性变异(PM1+PM2_Supporting+PP3_Moderate+PP4)。 结论 GALT基因c.627T>A(p.Y209*)和c.370G>C(p.G124R)复合杂合变异可能是患儿半乳糖血症的遗传学病因。上述发现扩展了GALT基因的变异谱。对无明显诱因出现贫血、喂养困难、黄疸、肝功能异常和凝血功能异常等症状的患者，应尽早行血尿代谢筛查，结合基因检测进行确诊。 Objective To explore the clinical features and genetic basis of a child with Galactosemia. Methods A child who had presented at the Children′s Hospital Affiliated to Zhengzhou University on November 20, 2019 was selected as the study subject. Clinical data of the child was collected. Whole exome sequencing was carried out for the child. Candidate variants were validated by Sanger sequencing. Results Clinical manifestations of the child have included anemia, feeding difficulty, jaundice, hypomyotonia, abnormal liver function and coagulation abnormality. Tandem mass spectrometry showed increased citrulline, methionine, ornithine and tyrosine. Urine organic acid analysis showed increased phenyllactic acid, 4-hydroxyphenylacetic acid, 4-hydroxyphenyllactic acid, 4-hydroxyphenylpyruvate and N-acetyltyrosine. Genetic testing revealed that the child has harbored compound heterozygous variants of the GALT gene, namely c. 627T>A (p.Y209*) and c. 370G>C (p.G124R), which were respectively inherited from her healthy parents. Among these, c. 627T>A (p.Y209*) was known as a likely pathogenic variant, while c. 370G>C (p. G124R) was unreported previously and also predicted as a likely pathogenic variant(PM1+ PM2_Supporting+ PP3_Moderate+ PP4). Conclusion Above discovery has expanded the spectrum of the GALT gene variants underlying Galactosemia. Patients with thrombocytopenia, feeding difficulties, jaundice, abnormal liver function and coagulation abnormality without obvious causes should be analyzed by screening of metabolic diseases in combination with genetic testing.

    半乳糖血症GALT基因变异

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    CHD7基因变异致特发性低促性腺激素型性腺功能减退症1例的临床特点与遗传学分析

    王忻邓茜王娟娟蔡文娟...
    847-850页
    查看更多>>摘要：目的 探讨1例CHD7基因变异所致嗅觉正常的特发性低促性腺激素性腺功能减退症(nIHH)患儿的临床及遗传学特征。 方法 以2022年10月就诊于安徽省儿童医院的1例nIHH患儿作为研究对象。对其进行全外显子组测序。对候选变异进行Sanger测序家系验证以及生物信息学分析。 结果 患儿主要表现为第二性征发育迟缓，但嗅觉功能未见异常。基因检测提示患者CHD7基因存在c.3052C>T(p.Pro1018Ser)杂合变异，其父母该位点均为野生型。该变异在PubMed及HGMD数据库均未见收录。同源性分析提示相关位点在进化中高度保守，蛋白质模拟分析提示可能破坏局部结构的稳定性。根据美国医学与遗传学学会变异指南，该变异评级为可能致病性变异(PS2+PM2_Supporting+PP2+PP3+PP4)。 结论 该患者第二性征发育迟缓表现可能缘于CHD7基因的变异。上述发现进一步拓展了CHD7基因的变异谱。 Objective To explore the clinical feature and genetic etiology of a patient with normosmic idiopathic hypogonadotropic hypogonadism (nIHH) due to variant of CHD7 gene. Methods A patient who had presented at Anhui Provincial Children′s Hospital in October 2022 was selected as the study subject. Clinical data of the patient was collected. The patient and his parents were subjected to trio-whole exome sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. Results The patient had featured delayed development of secondary sexual characteristics but normal olfactory function. Genetic testing revealed that he has harbored a c. 3052C>T (p.Pro1018Ser) missense variant of theCHD7 gene, for which both of his parents were of the wild type. The variant has not been recorded in the PubMed and HGMD databases. Analysis of amino acid sequences suggested that the variant site is highly conserved, and the variant may affect the stability of protein structure. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 3032C>T variant was classified as a likely pathogenic (PS2+ PM2_Supporting+ PP2+ PP3+ PP4). Conclusion The delayed development of secondary sexual characteristics of the patient may be attributed to the c. 3052C>T (p.Pro1018Ser) variant of theCHD7 gene. Above finding has expanded the variation spectrum of the CHD7 gene.

    特发性低促性腺激素型性腺功能减退症嗅觉正常的特发性低促性腺激素型性腺功能减退症特发性低促性腺激素性性腺功能减退症CHD7基因基因检测

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    以动眼神经麻痹为表现的2型神经纤维瘤病患者1例的临床特点及遗传学分析

    丁兴欢梁博梁庭毓李晶晶...
    851-855页
    查看更多>>摘要：目的 报告1例以动眼神经麻痹为首发症状的2型神经纤维瘤病(NF2)患者，并探讨其遗传学病因。 方法 选择2021年7月10日就诊于首都医科大学附属北京地坛医院的1例NF2患者作为研究对象。对患者及其父母进行全脑、全脊髓MRI检查，追溯其家族史，采集家系成员的外周血样，提取DNA并进行全外显子组测序。对候选变异进行Sanger测序家系验证。 结果 影像学检查显示患者存在双侧前庭神经鞘瘤、海绵窦区脑膜瘤、腘窝神经源性肿瘤、皮下多发结节等。基因测序证实其NF2基因第8外显子存在c.757A>T新发无义变异，导致第253位的赖氨酸替换为终止密码子，导致编码的Merlin蛋白从第253位以后的氨基酸丢失。该变异未见健康人群公共数据库收录，生物信息学软件预测其氨基酸序列高度保守。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(PVS1+PS2+PM2_Supporting+PP3+PP4)。 结论 该患者发病较早，症状不典型且较重，其遗传学病因为NF2基因c.757A>T(p.K253*)杂合无义变异。上述发现丰富了NF2基因的变异谱。 Objective To report on a rare case of Neurofibromatosis type 2 (NF2) manifesting as oculomotor nerve palsy and explore its genetic basis. Methods A patient with NF2 who had presented at Beijing Ditan Hospital Affiliated to Capital Medical University on July 10, 2021 was selected as the study subject. Cranial and spinal cord MRI was carried out on the patient and his parents. Peripheral blood samples were collected and subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing. Results MRI revealed bilateral vestibular Schwannomas, bilateral cavernous sinus meningiomas, popliteal neurogenic tumors, and multiple subcutaneous nodules in the patient. DNA sequencing revealed that he has harbored a de novo nonsense variant of the NF2 gene, namely c. 757A>T, which has replaced a codon (AAG) encoding lysine (K) at position 253 with a stop codon (TAG). This has resulted in removal of the Merlin protein encoded by theNF2 gene from position 253 onwards. The variant was not found in public databases. Bioinformatic analysis suggested that the corresponding amino acid is highly conserved. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+ PS2+ PM2_Supporting+ PP3+ PP4). Conclusion The heterozygous nonsense variant c. 757A>T (p.K253*) of theNF2 gene probably underlay the disease in this patient with an early onset, atypical but severe phenotype.

    2型神经纤维瘤病NF2基因全外显子组测序新发变异动眼神经麻痹

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    Schmid型干骺端软骨发育异常患儿1例的临床及分子遗传学分析

    董孝云郑璇林法涛方拴锋...
    856-859页
    查看更多>>摘要：目的 分析1例Schmid型干骺端软骨发育异常(SMCD)患儿的临床特征和基因型。 方法 收集于2021年10月就诊于郑州大学附属儿童医院的SMCD患儿的病史和家族史，并对其进行详细的临床检查。对患儿进行高通量测序分析，并用Sanger测序法对候选变异进行家系验证。 结果 全外显子组测序提示患儿的COL10A1基因存在c.1772G>A(p.C591Y)错义变异，Sanger测序证实其父母均未携带相同的变异，提示其为新发，在HGMD及ClinVar数据库中均未见该位点的记录。根据ACMG指南，判断其为可能致病性变异(PM2_Supporting+PM5+PM6+PP3+PP4)。 结论 COL10A1基因c.1772G>A(p.C591Y)变异可能为该SMCD患儿的遗传学病因，基因检测为该家系的遗传咨询和产前诊断提供了依据。该变异的发现丰富了COL10A1基因的变异谱。 Objective To analyze the clinical features and genotype of a child with Schmid type metaphyseal chondrodysplasia. Methods Clinical data of the child and her parents was collected. The child was subjected to high-throughput sequencing, and candidate variant was verified by Sanger sequencing of her family members. Results Whole exome sequencing revealed that the child has harbored a heterozygous c. 1772G>A (p.C591Y) variant of theCOL10A1 gene, which was not found in either of her parents. The variant was not found in the HGMD and ClinVar databases, and was rated as likely pathogenic(PM2_Supporting+ PM5+ PM6+ PP3+ PP4)based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Conclusion The heterozygous c. 1772G>A (p.C591Y) variant of theCOL10A1 gene probably underlay the Schmid type metaphyseal chondrodysplasia in this child. Genetic testing has facilitated the diagnosis and provided a basis for genetic counselling and prenatal diagnosis for this family. Above finding has also enriched the mutational spectrum of the COL10A1 gene.

    Schmid型干骺端软骨发育异常COL10A1基因基因变异新发变异

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    LARP7基因复合杂合变异所致1例Alazami综合征患者的临床及遗传学分析

    袁琳赵澎盛倩倩牟苇杭...
    860-864页
    查看更多>>摘要：目的 分析1例Alazami综合征(AS)患儿的临床表型及遗传学病因。 方法 以2021年6月15日就诊于天津市儿童医院的1例患儿作为研究对象。对其进行全外显子组测序(WES)分析，并对候选变异进行Sanger测序家系验证。 结果 WES检测提示患儿携带LARP7基因存在c.429_430delAG(p.Arg143Serfs*17)及c.1056_1057delCT(p.Leu353Glufs*7)移码变异，经Sanger测序验证分别遗传自其父母。 结论 LARP7基因c.429_430delAG及c.1056_1057delCT变异可能为该患儿的致病原因。 Objective To analyze the clinical phenotype and genetic basis of a child with Alazami syndrome (AS). Methods A child who presented at Tianjin Children′s Hospital on June 15, 2021 was selected as the study subject. The child was subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing. Results WES revealed that the child has harbored two frameshifting variants of the LARP7 gene, namely c. 429_430delAG (p.Arg143Serfs*17) and c. 1056_1057delCT (p.Leu353Glufs*7), which were verified by Sanger sequencing to be respectively inherited from his father and mother. Conclusion The compound heterozygous variants of the LARP7 gene probably underlay the pathogenesis in this child.

    Alazami综合征LARP7基因全外显子组测序

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    母源 PAK3新发剪接变异导致X连锁智力障碍1例患儿的分析

    王陈邱雪平胡绘靳冰玉...
    865-870页
    查看更多>>摘要：目的 探讨1例具有严重智力障碍和明显行为异常的患儿的遗传学病因。 方法 采集2020年12月2日就诊于武汉大学中南医院的1例具有智力障碍和行为异常患儿及其父母的外周血样，进行全外显子组测序，并通过Sanger测序对其家系成员进行共分离验证。采用短串联重复序列分析对患儿母亲携带的变异进行溯源，并通过minigene实验对剪接变异进行体外功能验证。 结果 全外显子组测序发现患儿携带母源性PAK3基因c.176-2A>G剪接变异。Sanger测序及短串联重复序列分析证实其母亲携带的变异为新发变异。Minigene实验结果证实其第2外显子存在异常剪接。根据美国医学遗传学与基因组学学会变异相关指南，该变异评级为致病性变异(PVS1+PS3+PM2_Supporting+PP3) 结论 PAK3基因c.176-2A>G变异可能是患儿的遗传学病因。上述发现丰富了PAK3基因的变异谱，为患儿家庭的遗传咨询和产前诊断提供了依据。 Objective To explore the genetic etiology for a child with profound intellectual disabilities and obvious behavioral abnormalities. Methods A male child who had presented at the Zhongnan Hospital of Wuhan University on December 2, 2020 was selected as the study subject. 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. Short tandem repeat (STR) analysis was carried out to determine its parental origin. The splicing variant was also validated in vitro with a minigene assay. Results WES results revealed that the child had harbored a novel splicing variant of c. 176-2A>G in thePAK3 gene, which was inherited from his mother. The results of minigene assay have confirmed aberrant splicing of exon 2. According to the guidelines from the American College of Medical Genetics and Genomics, it was classified as a pathogenic variant (PVS1+ PM2_Supproting+ PP3). Conclusion The novel splicing variant c. 176-2A>G of thePAK3 gene probably underlay the disorder in this chlid. Above finding has expanded the variation spectrum of the PAK3 gene and provided a basis for genetic counseling and prenatal diagnosis for this family.

    X连锁智力障碍全外显子组测序PAK3基因Minigene实验

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    近亲婚配所致D双功能蛋白缺乏症患儿1例的遗传学分析

    李立佳龙庆义温晓梅李雪...
    871-875页
    查看更多>>摘要：目的 分析1例由近亲婚配所致D双功能蛋白缺乏症(DBPD)患儿的遗传学病因。 方法 选取2022年1月6日因"肌张力低、全面发育落后"就诊于海南医学院第一附属医院的1例DBPD患儿作为研究对象，并收集其临床资料及其家系调查资料。提取患儿及父母、姐姐的外周血样，提取基因组DNA，应用全外显子组测序对患儿进行基因变异检测，对候选变异进行Sanger测序家系验证。应用生物信息软件预测变异位点的致病性，诊断患儿所患疾病。 结果 患儿为2岁9个月女性，临床表现为肌张力低下、发育迟缓、抬头不稳，感音神经性耳聋。血清长链脂肪酸增高，听性脑干诱发电位双侧耳90 dBnHL刺激均未能引出V波，头颅MRI提示胼胝体变薄，白质发育不良，患儿父母系近亲婚配，其长女表型正常，无D双功能蛋白缺乏症相关临床症状，其儿子出生当天频繁惊厥、肌张力低及喂养困难，生后1个半月夭折。基因测序结果显示患儿HSD17B4基因存在c.483G>T(p.Gln161His)纯合变异，父母、姐姐均携带HSD17B4基因c.483G>T(p.Gln161His)者。根据美国医学遗传学与基因组学学会变异评级相关指南，c.483G>T(p.Gln161His)变异评级为致病性变异(PM1+PM2_Supporting+PP1+PP3+PP4)。 结论 父母近亲婚配导致患儿HSD17B4基因携带c.483G>T(p.Gln161His)纯合变异，考虑为是患儿的遗传学病因。 Objective To explore the genetic etiology of a child with D bifunctional protein deficiency (DBPD) born to a consanguineous pedigree. Methods A child with DBPD who was admitted to the First Affiliated Hospital of Hainan Medical College on January 6, 2022 due to hypotonia and global developmental delay was selected as the study subject. Clinical data of her pedigree members were collected. Peripheral blood samples of the child, her parents and elder sisters were collected and subjected to whole exome sequencing. Candidate variant was validated by Sanger sequencing and bioinformatic analysis. Results The child, a 2-year-and-9-month-old female, had featured hypotonia, growth retardation, unstable head lift, and sensorineural deafness. Serum long-chain fatty acids were elevated, and auditory brainstem evoked potentials had failed to elicit V waves in both ears with 90 dBnHL stimulation. Brain MRI revealed thinning of corpus callosum and white matter hypoplasia. The child's parents were secondary cousins. Their elder daughter had a normal phenotype and no clinical symptoms related to DBPD. Elder son had frequent convulsions, hypotonia and feeding difficulties after birth, and had died one and a half month later. Genetic testing revealed that the child had harbored homozygous c. 483G>T(p.Gln161His) variants of theHSD17B4 gene, for which both of her parents and elder sisters were carriers. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 483G>T(p.Gln161His) was rated as a pathogenic variant (PM1+ PM2_Supporting+ PP1+ PP3+ PP4). Conclusion The homozygous c. 483G>T (p.Gln161His) variants of theHSD17B4 gene caused by the consanguineous marriage probably underlay the DBPD in this child.

    近亲D双功能蛋白缺乏症肌张力低下发育迟缓HSD17B4基因儿童

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    发育迟缓伴智力障碍患儿2例的遗传学分析

    王凤阳祁娜高越吴东...
    876-880页
    查看更多>>摘要：目的 明确2例发育迟缓/智力障碍(DD/ID)患儿的遗传学病因。 方法 选取分别于2021年8月29日以及2019年8月5日就诊于河南省人民医院的2例DD/ID患儿作为研究对象，收集患儿的临床资料，并应用微阵列比较基因组杂交技术(aCGH)对患儿及其父母的外周血样进行染色体拷贝数变异(CNV)分析。 结果 2例患儿分别为2岁10个月和3岁，均具有发育迟缓、智力障碍、头颅MRI异常等表现。aCGH检测患儿1结果为arr[hg19]6q14.2q15(84621837_90815662)×1，提示存在6.19 Mb缺失，所涉及的ZNF292基因的杂合变异可能导致常染色体显性智力发育障碍64。根据美国医学遗传学与基因组学学会(ACMG)相关指南评判为致病性CNV；患儿2的检测结果为arr[hg19]22q13.31q13.33(46294326_51178264)×1，提示存在4.88 Mb缺失，所涉及的SHANK3基因单倍剂量不足可能导致Phelan-McDermid综合征，评判为致病性CNV。2例患儿的父母检测结果均未见异常。 结论 染色体6q14.2q15缺失和22q13.31q13.33缺失可能分别是2例患儿发育迟缓和智力障碍的遗传学病因，ZNF292基因单倍剂量不足可能是导致6q14.2q15缺失患儿临床表型的关键因素。 Objective To explore the genetic etiology of two patients with developmental delay and intellectual disability. Methods Two children who were respectively admitted to Henan Provincial People′s Hospital on August 29, 2021 and August 5, 2019 were selected as the study subjects. Clinical data were collected, and array comparative genomic hybridization (aCGH) was carried out on the children and their parents for the detection of chromosomal microduplication/microdeletions. Results Patient 1 was a 2-year-and-10-month female and patient 2 was a 3-year-old female. Both children had featured developmental delay, intellectual disability, and abnormal findings on cranial MRI. aCGH revealed that patient 1 has harbored arr[hg19]6q14.2q15(84621837_90815662)×1, a 6.19 Mb deletion at 6q14.2q15, which encompassed ZNF292, the pathogenic gene for Autosomal dominant intellectual developmental disorder 64. Patient 2 has harbored arr[hg19] 22q13.31q13.33(46294326_51178264)×1, a 4.88 Mb deletion at 22q13.31q13.33 encompassing the SHANK3 gene, haploinsufficiency of which can lead to Phelan-McDermid syndrome. Both deletions were classified as pathogenic CNVs based on the guidelines of American College of Medical Genetics and Genomics (ACMG) and were not found in their parents. Conclusion The 6q14.2q15 deletion and 22q13.31q13.33 deletion probably underlay the developmental delay and intellectual disability in the two children, respectively. Haploinsufficiency of the ZNF292 gene may account for the key clinical features of the 6q14.2q15 deletion.

    DNA拷贝数变异6q14.2q15缺失Phelan-McDermid综合征ZNF292基因SHANK3基因发育迟缓智力障碍

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    同步扩增和鉴定中国人群 KIR基因有无的PCR-SSP方法的建立

    邓志辉甄建新张耿杨智超...
    881-886页
    查看更多>>摘要：目的 探讨建立同步扩增中国人群全部KIR基因和鉴定KIR基因有无的序列特异性引物-聚合酶链反应(PCR-SSP)方法。 方法 选取2015年1月至2015年11月在深圳市血液中心无偿献血的132份健康受试者的血样为研究对象。基于中国人群精细水平KIR等位基因的多态性和单核苷酸多态性(SNP)信息，参考IPD-KIR数据库，设计KIR基因特异性引物用于扩增16种KIR基因及2DS4-Normal、2DS4-Deleted 2种亚型；并采用KIR基因型已知样本，对每对PCR引物的特异性进行验证。在KIR基因的PCR扩增反应中，复合扩增人体生长激素(HGH)基因片段作为内对照，以防止PCR扩增出现假阴性结果。随机选取132份KIR基因型已知的健康受试者DNA样本进行盲检，验证该方法的可靠性。 结果 本研究设计和筛选出的KIR特异性引物，可鉴定相应的KIR基因，而且内对照条带和特异性扩增条带均清晰、明亮；采用本研究建立的鉴定KIR基因有无的PCR-SSP方法检测纳入研究的132份样本的盲检结果，与已知KIR基因型完全一致。 结论 本实验建立的KIR PCR-SSP方法，鉴定中国人群KIR基因的有无可获得准确、可靠的结果。 Objective To develop a polymerase chain reaction-sequence specific primer (PCR-SSP) method for simultaneous amplification and identification of the KIR genes among Chinese population. Methods Peripheral blood samples from 132 healthy donors who had given blood at Shenzhen Blood Center from January 2015 to November 2015 were selected as the study subjects. Based on the polymorphism and single nucleotide polymorphism (SNP) information of high-resolution KIR alleles in the Chinese population and the IPD-KIR database, specific primers were designed to amplify all the 16 KIR genes and the 2DS4-Normal and 2DS4-Deleted subtypes. The specificity of each pair of PCR primers was verified by using samples with known KIR genotypes. During PCR amplification of the KIR gene, co-amplification the fragment of human growth hormone (HGH) gene by multiplex PCR was used as the internal control to prevent false negative results. A total of 132 samples with known KIR genotypes were randomly selected for blind inspection to verify the reliability of the developed method. Results The designed primers can specifically amplify the corresponding KIR genes, with clear and bright bands for the internal control and KIR genes. The results of detection are fully consistent with the known results. Conclusion The KIR PCR-SSP method established in this study can yield accurate results for the identification of the presence or absence of KIR genes.

    杀伤细胞免疫球蛋白样受体序列特异性引物-聚合酶链反应KIR基因

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