Objective:To analyze the genomic variation characteristics of fetal with abnormal serological screening, and to further explore the value of copy number variation (CNV) detection technology in prenatal diagnosis of fetal with abnormal serological screening.Methods:7617 singleton pregnant women who underwent amniocentesis for prenatal diagnosis solely due to abnormal Down’s serological screening were selected. According to the results of serological screening, the patients were divided into high risk group, borderline risk group and single abnormal multiple of median (MOM) group. CMA and CNV-Seq were used to detect the copy number variation of amniotic fluid cell genomic DNA and combined with amniotic fluid cell karyotype analysis for prenatal diagnosis. Outpatient revisit combined with telephone inquiry was used for postnatal follow-up.Results:Among 7617 amniotic fluid samples, aneuploidy was detected in 138cases (1.81%) by CMA and CNV-Seq, 9 cases of aneuploid chimerism were detected by amniotic fluid cell karyotype analysis, and 203 cases of fetus carrying pathogenic and likely pathogenic CNV(P/LP CNV) were detected, the variant of uncertain significance (VUS) was detected in 437 cases (5.7%), the overall abnormal detection rate was 10.33%. The detection rate of aneuploidy by CMA and CNV-Seq in three group were 123 cases (2.9%), 13 cases (1.3%) and 2 cases (0.4%), respectively, and showing no significant difference ( χ2=7.469, P=0.024). The detection rate of pathogenic and likely pathogenic CNV in three group were 163cases (2.6%); 24 cases (2.6%) and 16 cases (3.3%), respectively, and showing no significant difference ( χ2=0.764, P=0.682). The CMA reported 2.9% (108/3729)P/LP CNV, and CNV-seq reported 2.4% (95/3888)P/LP CNV, both tests showed similar detective capabilities ( χ2=1.504, P=0.22). The most popular P/LP CNV in this cohort were Xp22.31 microdeletion, 16p13.11 microduplication /microdeletion, 22q11.21 microduplication /microdeletion. In fetuses with P/LP CNV CNV, 59 fetuses were terminated pregnancy, and 32 of 112 fetuses born had abnormal clinical manifestations. Non-medically necessary termination of pregnancy occurred in 11 fetuses carrying VUS CNV, 322 fetuses carrying VUS CNV were born, 4 of them presented abnormal clinical manifestations. Conclusion:Compared with the traditional chromosome karyotype, CMA and CNV-Seq can improve the detection rate of pathogenic and likely pathogenic CNV. CMA and CNV-seq can be used for first tier diagnosis of pregnant women in the general population with abnormal Down’s serological screening.

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.

The study was conducted to access the prognostic value of mixed lymphocyte reaction blocking factors (MLR-Bf) for the pregnancy outcome after lymphocyte immunization (LIT) in different kinds of patients with unexplained recurrent spontaneous abortion (URSA). Following LIT, the patients were divided into two groups according to the time when the miscarriage occurs (group 1: before the demonstration of embryonic cardiac activity; group 2: after the demonstration of embryonic cardiac activity) and the times of URSA (patients with two URSA and three or more URSA). We respectively compared the success rate in immunized patients who showed MLR-Bf with control in each group. For patients with two URSA, there was no significant difference between treatment group and control in each group; for patients with three or more URSA, the pregnancy outcome was significantly improved in treatment group in group 1 (67.2% vs 53.1%, P=0.0004). Whereas no significant difference was detected in group 2 (60.3% vs 56.6%, P=0.5684). The obtained data demonstrated that the presence of MLR-Bf is a good prognostic criterium for the pregnancy outcome in patients with three or more URSA who had never had the demonstration of embryonic cardiac activity after LIT.

Objective To explore the relationship of the distribution of methylenetetrahydrofolate reductase enzyme(MTHFR)C677Tand A1298 Cwith lung cancer in Han population in Henan.Methods The genotype of MTHFR was detected by PCR-RFLP method in 202 cases of lung cancer(cancer group)and 202 health volunteers(control group)to analyze the gene frequency and distribution of MTHFR C677 Tand A1298C.Results The frequencies of CC,CT and TT of MTHFR C677 Twere 26.7%,50.5%and 22.8%in cancer group,and 34.2%,55.4%and 10.4%in control group,showing significant differences in TT subtype(P0.05)and no significant differences in CC and CT subtypes between two groups(P0.05).The odds ratio was 2.542 for lung cancer in those carrying TT genotype,and 95%CI was from1.453 to 4.444.The frequencies of AA,AC and CC of A1298 Cwere 27.2%,52.5%and 20.3%in cancer group,and32.2%,50.5% and 17.3% in control group,showing no significant differences between two groups(P0.05).Conclusion The TT subtype of MTHFR C677 Tgene is obviously correlated with lung cancer and A1298 Cis not correlated with lung cancer.

OBJECTIVE:To explore the value of HLA-DRB1 gene in predicting the outcome of unexplained recurrent spontaneous abortion (URSA) treated with paternal lymphocyte alloimmunization therapy (PLAT) in Henan Hans.METHODS:Three hundred URSA patients were recruited. Following PLAT treatment, they were divided into two groups according to the outcome of pregnancy. Polymerase chain reaction sequence specific primer (PCR-SSP) were conducted to analyze the HLA-DRB1 gene.RESULTS:For those who have received PLAT treatment, the frequency of HLA-DRB1*11 was significantly lower in successfully treated cases than those with abortion (0.052 vs. 0.110, P < 0.05, OR=0448), whilst the frequency of HLA-DRB1*15 was significantly greater in the former (0.207 vs. 0.100, P < 0.05, OR=2.352).CONCLUSION:For patients who have received PLAT treatment, those with HLA-DRB1*15 are more likely to conceive that those with HLA-DRB1*11.

OBJECTIVE:To analyze CYP17A1 gene mutations in a child patient with 17 alpha-hydroxylase/17, 20-lyase deficiency (17OHD), and to review characteristics of CYP17A1 gene mutations in Chinese patients with 17OHD.METHODS:Clinical data were collected. PCR and DNA sequencing were performed to detect mutations in the patient.RESULTS:The patient has presented classical features of 17OHD including hypertension, hypokalemia, decreased sex hormones and plasma cortisol, and elevated blood adrenocorticotrophic hormone. A compound heterozygous mutation c.987C>A and c.985del was detected in the CYP17A1 gene, which resulted in two premature stop codons at positions 328 and 417.CONCLUSION:A compound mutation, c.987C>A and c.985del, has been identified in a patient with 17OHD. Among CYP17A1 gene mutations identified in Chinese patients, missence mutations have been most common, and exons 5 and 8 have been the mutation hotspots.