人肝细胞癌4号染色体高频率杂合子丢失的研究

目的 为克了生新的肝细胞（HCC）相关肿瘤抑制基因的供位点依据。方法 使用4号染色体的12个微卫星DNA多态性标志,分析了48例原发性HCC的杂合子丢失（LOH）。结果 44％（21／48）和63％3（30／48）的肿瘤组织中至少有1个位点的LOH分别发生在4p和4q。丢失图排列鉴定了两个独立的共同丢失片段（CDR）。第1个定位在4q22-q25的CDR位于D4S392和D4S1625位点之间;第2个定位在4q27-q31的CDR位于D4S1625和D4S1652位点之间。结论 至少有两个肿瘤抑制位点存在于4q.     

散发性结直肠癌D10S1265位点的杂合缺失分析

目的:染色体上某特定位点遗传物质的丢失是肿瘤发生中的常见现象,抑癌基因的杂合缺失是结直肠癌形成中的关键步骤之一.本实验通过对83例散发性结直肠癌中D10S1265位点杂合缺失的研究,探讨其在结直肠癌演变中的作用.方法:荧光标记的多态性微卫星引物D10S1265与83例结直肠癌的肿瘤和正常组织进行PCR反应.PCR产物在ABI Prism 377自动荧光测序仪电泳3h,以GeneScan3.1和Genotyper 2.1软件进行扫描以及杂合缺失分析.其结果与临床病理因素进行卡方检验.结果:D10S1265位点(10q24.3)的杂合缺失率是50.0%,肝转移的7例未发现LOH,无肝转移病例达58.97%(23/39,P=0.014),但与淋巴结转移无关.另外,此位点的杂合缺失与Dukes'分期显著相关(P=0.013),与其他临床病理因素无关.结论:D10S1265位点附近可能存在与散发性结直肠癌有关的抑癌基因,此基因与结直肠癌的进展和肝转移相关.     

Factors that influence parents’ experiences with results disclosure after newborn screening identifies genetic carrier status for cystic fibrosis or sickle cell hemoglobinopathy

Objective

Newborn screening (NBS) identifies genetic carriers for sickle cell hemoglobinopathy and cystic fibrosis. We aimed to identify factors during initial NBS carrier results disclosure by primary care providers (PCPs) that influenced parents’ experiences and reactions.

Methods

Open-ended responses from telephone interviews with 270 parents of carriers were analyzed using mixed-methods. Conventional content analysis identified influential factors; chi-square tests analyzed relationships between factors and parent-reported reactions.

Results

Parents reported positive (35%) or negative (31%) reactions to results disclosure. Parents’ experiences were influenced by specific factors: content messages (72%), PCP traits (47%), and aspects of the setting (30%). Including at least one of five specific content messages was associated (p < 0.05) with positive parental reactions; omitting at least one of four specific content messages was associated (p < 0.05) with negative parental reactions. Parents reported positive reactions when PCPs avoided jargon or were perceived as calm. Parents reported negative reactions to jargon usage and results disclosure by voicemail.

Conclusion

Parents identified aspects of PCP communication which influenced their reactions and results disclosure experiences.

Practice implications

Our findings suggest ways PCPs may improve communication of carrier results. PCPs should provide specific content messages and consider how their actions, characteristics, and setting can influence parental reactions.     

3种少见α地中海贫血点突变杂合取合予的临床特征

目的：了解3种少见α地中海贫血点突变[血红蛋白Constants Spring （Hb CS）,血红蛋白Westmead（Hb WS）和血红蛋白Quong Sze（Hb QS）]杂合子与双重杂合子的临床特征。方法：收集135例上述3种α-地中海贫血点突变的杂合子与双重杂合子患者和正常对照男女各20例,进行血常规参数分析、血红蛋白分析、等位基因特异性寡核苷酸探针反向斑点杂交方法（RDB）和多重跨越断裂点聚合酶链反应（PCR）方法检测基因型。结果：杂合子组、Hb CS和Hb WS双重杂合子（αCSα/αWSα）组均无临床表现,但Hb QS杂合子（αQSα/αα）组的红细胞平均体积（MCV）和红细胞平均血红蛋白（MCH）值小于其余杂合子组（P＜0.05）。Hb CS和Hb QS双重杂合子（αCSα/αQSα）组有轻微的临床表现,MCV和MCH值低于Hb CS杂合子和Hb WS杂合子组（P＜0.05）。结论：Hb CS杂合子组和Hb WS杂合子组表现为静止型地中海贫血,Hb QS杂合子组更接近轻型地中海贫血。双重杂合子表型多样,Hb CS和Hb WS双重杂合子表现接近于静止型地中海贫血,而Hb CS和Hb QS双重杂合子表现类似中间型α地中海贫血（Hb H病）,在遗传咨询中需注意。     

G6PD比值法检测葡萄糖-6-磷酸脱氢酶基因突变女性杂合子影响因素的研究

目的确定G6PD/6PGD比值法在检测葡萄糖-6-磷酸脱氢酶缺乏的女性杂合子时的最佳实验条件,提高对葡萄糖-6-磷酸脱氢酶缺乏的女性杂合子的检出率。方法(1)应用突变特异性扩增系统确定女性杂合子的基因突变型。(2)G6PD/6PGD定量比值法。结果根据试验结果进行统计分析及ROC曲线得出最佳实验条件为孵育温度为37℃,底物浓度为0.78mmol/LG6PNa2及0.195mmol/LNADP ,反应时间为10min。结论G6PD/6PGD比值法在最佳实验条件下,能大大提高对G6PD基因突变女性杂合子的检出率。     

荧光原位杂交技术不同方案用于染色体易位携带者胚胎植入前遗传学诊断的效率比较

目的 探讨荧光原位杂交(FISH)技术不同方案用于染色体易位携带者胚胎植入前遗传学诊断(PGD)的效率.方法 根据FISH检测方案的不同进行分组:采用全染色体涂抹探针对染色体易位携带者8个周期的109个卵母细胞第一极体进行诊断(A组),采用联合端粒和着丝粒探针对染色体易位携带者29个周期的357个卵裂球进行诊断(B组),比较两组的活检成功率、固定时细胞丢失率、无核细胞数等.结果 A组的109个卵母细胞中72个受精,受精率为66.1%(72/109),B组的357个卵裂球中304个受精,受精率为85.2%(304/357),A组的受精率显著低于B组,差异有统计学意义(P<0.05).固定时细胞丢失率A组为9.6%(12/104),B组为1.6%(4/252),两组比较,差异也有统计学意义(P<0.05).杂交后核的无信号率A组为11.2%(10/89),B组为3.0%(7/233),两组比较,差异有统计学意义(P<0.05).A组的诊断率为72.5%(79/109),显著低于B组的89.8%(230/256),差异有统计学意义(P<0.05).A组的临床妊娠率和胚胎植入率分别为3/7和22.2%(4/18),均高于B组的30.4%(7/23)和15.7%(8/51),但差异均无统计学意义(P>0.05).结论 FISH两种方案均可有效地进行染色体平衡易位的PGD,卵裂球PGD的诊断效率更高.     

血清铜蓝蛋白检测在肝豆状核变性及其携带者中的临床意义

目的肝豆状核变性(hepatolenticular degeneration)又称为Wilson病(Wilson’s disease,WD)。目前对于铜蓝蛋白在WD、WD携带者及病毒性肝炎的诊断价值尚不一致。文中探讨检测血清铜蓝蛋白在WD、WD携带者和病毒性肝炎中的临床意义,研究WD携带者的临床表现和铜代谢规律。方法确诊的WD患者60例,WD携带者30例,合并病毒性肝炎的WD携带者2例,病毒性肝炎患者20例,健康对照者20例。对所有入组者进行病史采集、临床神经系统检查,检测血清铜蓝蛋白水平以及铜代谢指标检查,包括脑脊液铜、血清铜、青霉胺排铜试验前后24 h尿铜。同时进行神经影像学、腹部B超、肝功能、肝炎标志物检查。结果 WD患者铜蓝蛋白水平低于健康人,排铜试验后尿铜显著高于健康人。WD携带者铜蓝蛋白异常者高达73%,其铜蓝蛋白水平介于健康人和WD患者之间。合并病毒性肝炎的WD携带者铜蓝蛋白水平低于0.1 g/L且随肝功能波动,其尿铜略高于健康人,排铜试验后尿铜高于健康人。单纯病毒性肝炎患者铜蓝蛋白水平仅轻度降低。结论血清铜蓝蛋白水平有助于鉴别WD、WD携带者和其他肝病。病毒性肝炎多导致铜蓝蛋白水平轻度异常;WD携带者合并病毒性肝炎时,铜蓝蛋白水平显著下降。WD携带者的铜蓝蛋白水平常介于健康人和WD患者之间,可作为WD携带者的诊断依据。WD携带者存在轻微铜代谢异常,但无临床症状,不需进行排铜治疗。     

Human leukocyte antigen class II alleles and natural history of HPV 2/27/57-induced common warts

Epidemiological studies have demonstrated an association between HLA-DQB1*03 alleles and the risk of cervical cancer induced by human papillomavirus (HPV). As persistence of HPV infection is required for developing cervical cancer, we wanted to elucidate the role of HLA-class II allele polymorphisms in the persistence of common warts induced by HPV 2, HPV 27 or HPV 57. Therefore, we determined the distribution of HLA-DQA1, -DQB1, and -DRB1 alleles in 71 patients presenting with HPV 2/27/57-induced common warts which had persisted for at least 18 months as well as in 92 individuals who had never suffered from common warts or whose warts had healed in less than 18 months. Among patients with long-lasting warts, the carriership frequencies and allele frequencies of DQA1*0301, DQB1*0301, DRB1*07 and DRB1*09 were higher, and the allele frequencies of DQA1*0501, DQB1*0603, DRB1*01 and DRB1*03 were lower. Statistically significant differences (Bonferroni adjusted Fishers exact test) were found for carriership frequency of DQA1*0301 (46.5 vs 21.7%, P=0.013) and for carriership frequency (18.3 vs 1.1%, P=0.0015) and allele frequency (12 vs 0.5%, P=0.000013) of DQB1*0301. A greater proportion of patients with long-lasting warts than of subjects without persistent warts were homozygous at the DQA1 (14.1 vs 6.5%) and DQB1 (16.9 vs 8.6%) gene loci. These results suggest that the natural history of cutaneous HPV 2/27/57-induced common warts may be modulated by allele polymorphisms at the HLA-DQA1 and HLA-DQB1 gene loci.     

凝血因子V169G→A基因突变的研究分析

目的 研究分析中国新疆地区健康人群中FV1691G→A基因突变的发生率。方法 凝血因子V(coagulation factor V)在凝血过程中是一种重要的辅因子,其基因中一个点突变1691G→A,使它对抗凝血系统中的一种血浆蛋白质C(APC)的失活作用而产生抗性,从而使血栓发生风险增大。应用多聚酶链反应-限制性片段长度多态性分析(PCR-RFLP),对新疆地区98例汉族、67例维吾尔族和54例哈萨克族健康个体进行研究分析。结果 哈萨克族人群中检出2例FV Leiden 1691G→A突变杂合子;汉族和维吾尔族人群中均未发现该突变类型。结论 中国新疆地区哈萨克族人群中存在FV Leiden基因突变,而汉族和维吾尔族人群中未检测到该类型突变,FV Leiden的发生存在着地区、种族差异,FV Leiden突变可能不是新疆地区人群静脉血栓(VT)发病的主要危险因素。     

Fabry's Disease: Detection of Heterozygotes Using Blastoid Lymphocytes StimuIated by PhytohemaggIutinin

Cultured lymphocytes with phytohemagglutinin (PHA) were used for samples of α-galactosidase (α-gal) assay. In control subjects α-gal activity of cultured lymphocytes with PHA increased compared to that of uncultured or cultured lymphocytes without lectin. While the carrier females of Fabry's disease showed a slight decrease of α-gal activity in cultured lymphocytes with PHA. Therefore, heterozygotes could be definitely distinguished from controls. Cultured lymphocytes with PHA were thought to be available for the detection of heterozygotes.