对一出生表现为缺血缺氧性脑病患者进行了遗传学诊断和病因分析.运用MRI技术对患儿脑部进行检查,运用常规G显带核型分析技术对患儿及其父母染色体核型进行分析,运用染色体芯片分析技术(CMA)对患儿及其父母全基因组进行染色体拷贝数变异分析,对多余染色体进行鉴定及定位.MRI检测结果支持患儿缺血缺氧性脑病诊断,并发现Dandy-Walker畸形表现.核型分析结果显示患儿母亲染色体核型为46,XX,t(10;13)(p11.1;q11)[11]/46,XX[19].患儿父亲染色体核型结果正常.患儿染色体核型为47,XX,+mar.患儿父母CMA检测结果显示不存在200 kb以上拷贝数变异(CNVs).患儿CMA检测结果显示10号染色体p15.3p11.1区域发生了3拷贝重复,片段大小为38.39 Mb.该研究发现一罕见10号染色体小额外标记染色体(sSMC),对其遗传方式及致病性进行了分析,认为sSMC(10)是该患者的致病原因.

目的:探讨基因组拷贝数变异测序(CNV-Seq)技术联合短串联重复序列(STR)分型对早期自然流产查因的可行性和应用价值,为早期自然流产发生后的再次妊娠提供遗传学的风险评估.方法:选取河南省人民医院医学遗传研究所收集到的545例早期自然流产组织,使用基于高通量测序技术的CNV-Seq平台和基于荧光标记复合扩增的STR分型技术对染色体异常进行联合分析,并使用单核苷酸多态性芯片(SNP-array)对部分特殊异常结果进行验证.结果:CNV-Seq技术联合STR分型成功检测了545例样本,总阳性检出率为55.1％,包括染色体数目异常271例,结构异常23例,单亲二倍体6例.其中联合STR分型额外检出三倍体、单亲二倍体样本及其他染色体数目异常39例.SNP-array平台对6例单亲二倍体样本的验证结果与STR分型检出结果一致.结论:CNV-Seq技术联合STR分型检测可提高染色体异常的阳性检出率,为更准确分析早期自然流产的原因提供依据.

Objective To clarify the pathogenic mutations and provide references for prevention and treatment strategies and prenatal diagnosis by gene detection in 3 pedigrees with autosomal dominant polycystic kidney disease (ADPKD). Methods The family history and clinical data of 3 ADPKD pedigrees who admitted to our department of urology during 2017 and 2020 were collected in this study. The peripheral blood samples of these family members were harvested for DNA extraction. Targeted amplification and high-throughput sequencing was used to screen suspected pathogenic mutations in probands, and then these obtained mutations were verified and analyzed in the probands and their family members by Sanger sequencing. The pathogenicity of these mutations was analyzed with bioinformation analysis and the evaluation criteria of the American Society of Medical Genetics. Results Ultrasound examination showed that all the probands from the 3 families had polycystic kidneys, at the clinical stages of G1, G3a, and G5 respectively. The deletion frameshift mutation c.5933delA (p.Asn1978fs), nonsense heterozygous mutation c.6871C>T (G2291X) and deletion frameshift mutation of c.894_897delCCCT (p.299Sfs*34) in polycystic kidney disease 1 (PKD1) gene were detected in pedigrees 1, 2 and 3, respectively. The above variants in the 3 families were in line with phenotype-genotype separation. Conclusion We identify the pathogenic variants in the 3 pedigrees of hereditary polycystic kidney disease, among which c.5933delA and c.894_897delCCCT are new mutations, and c.6871C>T is a known pathogenic mutation.

目的 分析1例发育迟缓患儿的遗传学原因,探讨其染色体DNA拷贝数变异与表型的相关性.方法 发育迟缓患儿1例,应用常规G显带核型分析患儿及其父母的染色体核型,应用微阵列比较基因组杂交技术分析患儿及其父母DNA拷贝数变异,并对核型分析结果进行精确定位.结果 常规G显带核型分析示该患儿父母染色体核型正常,患儿为46,XX,del(18) (p11.2);微阵列比较基因组分析示患儿父母基因芯片检测结果正常,患儿18号染色体部分缺失,缺失区域为18p11.32-p11.21,片段大小为11.49 Mb.结论 微阵列比较基因组杂交技术分辨率和准确性高,可对染色体微变异进行精确定位;18号染色体短臂部分缺失可能与患儿发育迟缓有关.

目的 从基因水平分析河南地区汉族人群人类白细胞抗原HLA-DRB1等位基因型和频率,并了解其多态性分布状况.方法 通过聚合酶链式反应-序列特异性引物(PCR-SSP)方法对1730名河南籍汉族健康人群进行DRB1等位基因分型.结果 共检出13种DRB1等位基因型,频率最高的等位基因型为DRB1*15(18.12％),频率最低的等位基因型为DRB1*10(1.33％).与湖北、广东和吉林三省比较,河南汉族人群DRB1各等位基因型频率分布与吉林省汉族人群最为相似,只有DRB1*03、DRB1*12、DRB1* 13、DRB1* 14和DRB1* 16五个等位基因型频率存在显著统计学差异(P＜0.05);与湖北省有8个等位基因型频率存在显著统计学差异(P＜0.05);与广东省有9个等位基因型频率存在显著统计学差异(P＜0.05).结论 在河南省与湖北、广东、吉林三省汉族人群DRB1位点多态性的比较中,河南汉族人群DRB1等位基因型频率分布与吉林省汉族人群最相似;高频率的DRB1* 15等位基因型提示河南汉族人群可能易发生药物性肝损害.

Objective To analyse the effect of progesterone on peripheral blood corticotropin releasing hormone ( CRH ) and delivery time in women with premature rupture of membranes ( PROM ) .Methods 80 patients who were diagnosed with PROM in Department of Obstetrics and Gynecology, China Medical University were collected.Randomly divided into dexamethasone (DEX) group, dexamethasone plus progesterone (DEX+P) group, progesterone ( P) group and control group, three groups were detected on admission, admission 24 h, 48 h on peripheral white blood cell count, C-reaction protein, CRH level and time of delivery, neonatal weight, and analysis of CRH the level of the correlation and delivery time.Results Compared with the other three groups, the level of CRH in peripheral blood of DEX group were higher (P<0.05);CRH (P<0.05) increased faster;shorter delivery time (P<0.05); the level of CRH was negatively correlated with delivery time (r=-0.832, P<0.05).The results were statistically significant.Conclusion Dexamethasone treatment can make the premature rupture of fetal membranes of peripheral blood CRH levels rise, shorten the delivery time, progesterone can inhibit this process.

Objective To explore the possible roles of retinoic acid receptor-β(RAR-β)gene and death-associated protein kinase(DAPK)gene in esophageal squamous cell carcinoma(ESCC)and the value to the early diagnosis by observing hypermethylation status of RAR-βand DAPK genes.Methods Real-time quantitative methylation-specific PCR was adopted to detect the methylation status of RAR-βgene and DAPK gene promoter in 95cases of ESCC tissues(ESCC group),normal adjacent tissue(adjacent group)and normal tissue(control group).Results The methylation rates were46.3%,26.3% and 11.6% respectively in RAR-βgene promoter CpG island,and were 47.3%,22.1% and 12.6%respectively in DAPK gene promoter CpG island in ESCC group,adjacent group and control group.The methylation rates of RAR-βand DAPK genes were significantly higher in ESCC group than those in adjacent group and control group(P0.05).The methylation of RAR-βgene showed a difference in the ages of patients(P0.05),and the methylations of RAR-βand DAPK genes showed no significant difference in the location of tumor,or the degrees of differentiation,metastasis and infiltration(P0.05)in ESCC group.Conclusions Hypermethylations of RAR-βand DAPK genes are one of the epigenetic changes of ESCC,and may be involved in the development and progression of ESCC.

对象与方法 2011年1月至2012年7月来本所遗传咨询门诊就诊的143例原发性闭经患者.社会性别及外生殖器表现为女性.年龄13~27岁.主要.临床表现:五月经来潮、发育迟缓、B超示无子宫或幼稚子宫、两性畸形等.采集外周血用1640培养基进行淋巴细胞培养,常规方法收获细胞、制片,G-显带.使用Cytovision软件分析制备良好的中期分裂相30个.染色体核型按<人类细胞遗传学国际命名体制>(ISCN2005)分析.

Objective To investigate the correlation between the HLA-DQB1 and DRB1 gene and susceptibility of leukemia in Han nationality in Henan.Methods Polymerase chain reaction-specific sequence primers(PCR-SSP) method was used to HLA typing in the 52 patients with leukemia and 52 normal subjects as control.Results The frequencies of allele HLA-DRB104 in patients with leukemia were higher than those in control group(RR=3.6,χ2 =4.727,P0.05);while the frequencies of allele HLA-DRB111 notably decreased.(RR=0.319,χ2 =4.230,P0.05).Conclusion HLA-DRB104 allele in Han population in Henan province seems to contribute to susceptibility to leukemia,while HLA-DRB111 allele seems to be resistant to leukemia.

Objective To explore the relativity of chromosome abnormalities in malignant lymphoma(ML) and its relevance to histopathology.Methods The cytogenetic study on 24 patients with ML by the methods of short term culture to prepare the chromosome from peripheral blood.Results Mitotic cells that could be used for analysis were found in 23 cases.It showed that the numerical and/or structural abnormalities of clone chromosome were found in all patients with ML and were often involved in chromosomes 1,2,3,5,6,8,13,14,15,17,18,21 and X.The chromosome aberrations were associated with the histopathological type of ML in some extent.The hyperdiploid and hypodiploid of chromosome were mostly seen in patients with Non-Hodgin's lymphoma(NHL),whereas the polyploid and hyperdiploid and pseudodiploid were mostly seen in Hodgkin's disease(HD).Many structure aberrations of chromosome involved in 17p、1p、1q、2p、2q,which suggested that the structure deletion and breakpoint region should be associated with ML.Conclusions The combination of the cytogenetic and pathologic study could be benefit to classification,pathogenesis,diagnosis,treatment and prognosis of ML.