葡萄糖激酶W257R突变致青少年发病的成人型糖尿病一家系分析

青少年发病的成人型糖尿病（MODY）是一类以常染色体显性模式遗传的单基因疾病，临床表现以无症状、轻度空腹血糖升高为特征，很少出现糖尿病并发症。本文报道一例中国人群中葡萄糖激酶（GCK）基因新发W257R突变所致的MODY。在先证者及父亲、弟弟中均发现GCK基因（Chr744187343）第7号外显子的杂合突变c.769T>C（p.W257R）。该家系中W257R突变在中国人群中为首发。     

Variation near the hepatocyte nuclear factor (HNF)-4α gene associates with type 2 diabetes in the Danish population

Aims/hypothesis The hepatocyte nuclear factor (HNF)-4 is an orphan nuclear receptor, which plays crucial roles in regulating hepatic gluconeogenesis and insulin secretion. The gene encoding HNF-4 (HNF4A) is located on chromosome 20q12–q13 in a region that in several studies has shown linkage with type 2 diabetes. Recently, two independent studies identified single nucleotide polymorphisms (SNPs) in a 90-kb region spanning HNF4A, which showed strong association with type 2 diabetes in the Finnish and Ashkenazi Jewish populations. In an attempt to replicate and extend these findings, we selected four SNPs in the same HNF4A region, which in the Finnish and Ashkenazi Jewish populations were associated with type 2 diabetes, and examined their relationships with type 2 diabetes and prediabetic phenotypes in the Danish Caucasian population.Methods The rs1884614, rs2425637, rs1885088 and rs3818247 were analysed in case-control studies of 1387, 1429, 1417 and 1371 type 2 diabetic patients and 4766, 4727, 4665 and 4748 glucose-tolerant subjects respectively. Genotype–quantitative trait analyses comprised 4430, 4394, 4336 and 4413 middle-aged glucose-tolerant subjects from the population-based Inter99 cohort for the rs1884614, rs2425637, rs1885088 and rs3818247 respectively.Results The risk allele of the rs1884614, which is located 4 kb upstream of the HNF4A P2 promoter, was associated with type 2 diabetes (odds ratio [OR]=1.14, p=0.02) and with a subtle increase in post-OGTT plasma glucose levels in glucose-tolerant subjects (additive model, p=0.05).Conclusions/interpretation Consistent with results from studies of Finnish and Ashkenazi Jewish subjects, variation near the P2 region of HNF4A is associated with type 2 diabetes in the Danish population.     

新疆地区4000例遗传咨询患者细胞遗传学分析

目的统计遗传咨询患者染色体异常的类型和发生概率,研究细胞遗传学检查在临床诊断中的应用价值。方法采用常规外周血淋巴细胞培养及染色体制备,G显带,镜下核型分析。结果4000例遗传咨询患者中共检出染色体异常核型540例,检出率为13.50％。其中唐氏综合征92例,占总数的2.30％;特纳综合征22例,占总数的0.55％;平衡易位38例,占总数的0.95％;罗氏易位12例,占总数的0.30％;染色体倒位76例,占总数的1.90％;常染色体多态性变异216例,占总数的5.40％;Y染色体多态性变异70例,占总数的1.75％;另见染色体部分缺失6例,标记染色体3例,衍生染色体2例。结论染色体核型分析结果是临床诊断及优生优育的重要参考依据;进行遗传咨询、产前筛查和产前诊断可有效降低出生缺陷。     

Congenital Heart Disease as a Warning Sign for the Diagnosis of the 22q11.2 Deletion

Background

To alert for the diagnosis of the 22q11.2 deletion syndrome (22q11.2DS) in patients with congenital heart disease (CHD).

Objective

To describe the main CHDs, as well as phenotypic, metabolic and immunological findings in a series of 60 patients diagnosed with 22q11.2DS.

Methods

The study included 60 patients with 22q11.2DS evaluated between 2007 and 2013 (M:F=1.3, age range 14 days to 20 years and 3 months) at a pediatric reference center for primary immunodeficiencies. The diagnosis was established by detection of the 22q11.2 microdeletion using FISH (n = 18) and/or MLPA (n = 42), in association with clinical and laboratory information. Associated CHDs, progression of phenotypic facial features, hypocalcemia and immunological changes were analyzed.

Results

CHDs were detected in 77% of the patients and the most frequent type was tetralogy of Fallot (38.3%). Surgical correction of CHD was performed in 34 patients. Craniofacial dysmorphisms were detected in 41 patients: elongated face (60%) and/or elongated nose (53.3%), narrow palpebral fissure (50%), dysplastic, overfolded ears (48.3%), thin lips (41.6%), elongated fingers (38.3%) and short stature (36.6%). Hypocalcemia was detected in 64.2% and decreased parathyroid hormone (PTH) level in 25.9%. Decrease in total lymphocytes, CD4 and CD8 counts were present in 40%, 53.3% and 33.3%, respectively. Hypogammaglobulinemia was detected in one patient and decreased concentrations of immunoglobulin M (IgM) in two other patients.

Conclusion

Suspicion for 22q11.2DS should be raised in all patients with CHD associated with hypocalcemia and/or facial dysmorphisms, considering that many of these changes may evolve with age. The 22q11.2 microdeletion should be confirmed by molecular testing in all patients.     

PentaD、PentaE基因座基因频率在军人主、被动攻击行为群体分布的比较

目的通过比较PentaD、PentaE基因座等位基因及基因型频率在军人主、被动攻击行为群体中的分布,来推测与主、被动攻击行为发生相关的遗传因素。方法采用PCR结合毛细管电泳的方法对华东地区273例男性军人主动攻击行为者与163例男性军人被动攻击行为者进行PentaD、PentaE基因座的基因型分析,观察两组在PentaD、PentaE基因座的等位基因及基因型分布差异。结果PentaD、PentaE基因座均符合Hardy-Weinberg平衡;PentaE基因座基因型频率在主、被动军人攻击行为群体分布差异有统计学意义（P〈0．01）;单因素分析显示两组在PentaE基因座的基因型16-18的频率分布差异有统计学意义（P=0．0001）;PentaE基因座等位基因频率及PentaD基因座等位基因频率和基因型频率在两个群体中分布差异均无统计学意义（P〉0．05）。结论PentaE基因座可能与攻击行为的发生有关;在人攻击行为群体中PentaE基因座的基因型16-18为被动攻击行为的易感因素。     

Chromosomal and Genetic Analysis of a Human Lung Adenocarcinoma Cell Line OM

Background:

Lung cancer has become the leading cause of death in many regions. Carcinogenesis is caused by the stepwise accumulation of genetic and chromosomal changes. The aim of this study was to investigate the chromosome and gene alterations in the human lung adenocarcinoma cell line OM.

Methods:

We used Giemsa banding and multiplex fluorescence in situ hybridization focusing on the human lung adenocarcinoma cell line OM to analyze its chromosome alterations. In addition, the gains and losses in the specific chromosome regions were identified by comparative genomic hybridization (CGH) and the amplifications of cancer-related genes were also detected by polymerase chain reaction (PCR).

Results:

We identified a large number of chromosomal numerical alterations on all chromosomes except chromosome X and 19. Chromosome 10 is the most frequently involved in translocations with six different interchromosomal translocations. CGH revealed the gains on chromosome regions of 3q25.3-28, 5p13, 12q22-23.24, and the losses on 3p25-26, 6p25, 6q26-27, 7q34-36, 8p22-23, 9p21-24, 10q25-26.3, 12p13.31-13.33 and 17p13.1-13.3. And PCR showed the amplification of genes: Membrane metalloendopeptidase (MME), sucrase-isomaltase (SI), butyrylcholinesterase (BCHE), and kininogen (KNG).

Conclusions:

The lung adenocarcinoma cell line OM exhibited multiple complex karyotypes, and chromosome 10 was frequently involved in chromosomal translocation, which may play key roles in tumorigenesis. We speculated that the oncogenes may be located at 3q25.3-28, 5p13, 12q22-23.24, while tumor suppressor genes may exist in 3p25-26, 6p25, 6q26-27, 7q34-36, 8p22-23, 9p21-24, 10q25-26.3, 12p13.31-13.33, and 17p13.1-13.3. Moreover, at least four genes (MME, SI, BCHE, and KNG) may be involved in the human lung adenocarcinoma cell line OM.     

应用细菌人工染色体技术体外繁殖人巨细胞病毒

目的体外快速繁殖人巨细胞病毒（ HCMV）。方法用试剂盒抽提、纯化重组HCMV细菌人工染色体（BAC）,以重组HCMV细菌人工染色体（BAC-HCMV）为模板扩增UL82基因,酶切后连接至pcDNA载体,构建pcDNA-pp71重组质粒,转化感受态宿主菌,抽提及鉴定重组质粒。通过电穿孔技术将BAC-HCMV与鉴定成功的pcDNA-pp71重组质粒共转染人包皮成纤维细胞,通过多重PCR法及观察细胞病变效应、绿色荧光蛋白等方法鉴定培养后获得的HCMV。结果（1）获得pcDNA-pp71重组质粒,经PCR及双酶切后,片段大小与预期相符,进一步测序鉴定成功。（2） BAC-HCMV与pcDNA-pp71共转染人包皮成纤维细胞,出现细胞病变效应,经荧光显微镜观察可见绿色荧光。（3）以培养出的病毒DNA为模板进行多重PCR扩增,获得两条与预期大小相符的条带,鉴定HCMV体外繁殖成功。结论应用BAC技术成功在体外快速繁殖HC-MV,为HCMV研究提供实验材料,也为进一步研究HCMV分子机制奠定基础。     

超声诊断胎儿脉络丛囊肿的临床意义探讨

目的 探讨胎儿脉络丛囊肿对妊娠结局及临床预后的影响,为产前诊断提供更大帮助.方法 分析2011年1月至2014年3月在我院确诊的220例脉络丛囊肿胎儿的超声表现及相关临床资料.结果 220例脉络丛囊肿胎儿中,双侧77例,占35％;单侧143例,占65％.胎儿孤立性脉络丛囊肿199例随访未发现异常;胎儿复杂性脉络丛囊肿21例,其中6例染色体核型异常,5例为18-三体,1例为21-三体.结论 临床应对超声诊断复杂性脉络丛囊肿者在孕中期行胎儿染色体核型检查;对孤立性脉络丛囊肿可不干预.     

滇西地区1512例不明原因不良孕产女性患者染色体分析

目的 探讨原因不明的不良孕产女性患者与异常染色体核型的关系,为进一步寻求临床治疗提供理论依据.方法 回顾性比较分析大理大学第一附属医院自2013年8月至2016年10月接受检查的1512例不良孕产女性患者的检查染色体核型,采用外周血淋巴细胞培养,常规制片及G显带,对每个受检者计数50个核型,分析5个G显带核型.异常者分析核型10个以上.必要时行C和R显带分析.结果 1512例女性患者染色体检查,染色体异常62例,占4%,其中染色体结构异常57例,占91.94%(57/62),成为了异常染色体的主要部分;其分布为性染色体结构异常3例,占4.84%(3/62),常染色体结构异常54例,占87.10%(54/62).数目异常5例,占8.06%(5/62),其中性染色体1例,占1.61%,常染色体4例,占6.45%.结论 原因不明的不良孕产女性患者染色体核型分析能有效地检出异常染色体核型,对于诊断病因、干预以及靶向治疗有着十分重要的作用.