The frequency of chromosome anomalies in human preimplantation embryos after in-vitro fertilization

Previous studies have reported chromosome aberrations in humanpre-embryos after in-vitro fertilization (IVF). Although thereason for these abnormalities is not clear, there is evidencethat they can arise during gametogenesis, fertilization or cleavage.The present study has examined further the incidence of chromosomeabnormalities in human pre-embryos after IVF, using oocytesrecovered from normal volunteer women and from women undergoinginfertility treatment in an embryo-replacement programme. Chromosomepreparations were performed for 75 pre-embryos. Of these 35(47%) gave at least one metaphase in which analysis was possible.The overall incidence of abnormal pre-embryos was 40% (14/35).The absolute frequency of aberrations was 9% for trisomies,3% for polyploidies, 26% for structural anomalies and 3% forhypodiploidies. Five pre-embryos were found to be mosaics, threeof which had each one trisomic metaphase. In five of the pre-embryosmultiple anomalies were found. In 13 of the 14 abnormal pre-embryosthe aberrations were found in only one metaphase. The presentstudy demonstrates that trisomic mosaicism may not be a rareevent in human pre-embryos. Further evidence is provided thatmitotic non-disjunction is important for the production of aberrationsin human pre-embryos     

Premature ovarian failure

Premature ovarian failure (POF) causing hypergonadotrophic hypogonadism occurs in 1% of women. In majority of cases the underlying cause is not identified. The known causes include: (a) Genetic aberrations, which could involve the X chromosome or autosomes. A large number of genes have been screened as candidates for causing POF; however, few clear causal mutations have been identified. (b) Autoimmune ovarian damage, as suggested by the observed association of POF with other autoimmune disorders. Anti-ovarian antibodies are reported in POF by several studies, but their specificity and pathogenic role are questionable. (c) Iatrogenic following surgical, radiotherapeutic or chemotherapeutic interventions as in malignancies. (d) Environmental factors like viral infections and toxins for whom no clear mechanism is known. The diagnosis is based on finding of amenorrhoea before age 40 associated with FSH levels in the menopausal range. Screening for associated autoimmune disorders and karyotyping, particularly in early onset disease, constitute part of the diagnostic work-up. There is no role of ovarian biopsy or ultrasound in making the diagnosis. Management essentially involves hormone replacement and infertility treatment, the only proven means for the latter being assisted conception with donated oocytes. Embryo cryopreservation, ovarian tissue cryopreservation and oocyte cryopreservation hold promise in cases where ovarian failure is foreseeable as in women undergoing cancer treatments.     

Cytogenetic studies of familial and sporadic Alzheimer disease

We present cytogenetic findings in 7 familial and 5 sporadic Alzheimer disease (AD) patients and 34 unaffected relatives, spouses, and normal controls. Our study was prompted by reports of increased chromosome abnormalities in patients and family members at risk for AD. Coded peripheral blood chromosome preparations were evaluated for aneuploidy, aberration rates, and banding patterns. Statistical analyses of our results showed no increase in aneuploidy or aberrations in AD patients, their relatives, or normals. Chromosome loss or gain in aneuploid cells was not specific except in two individuals. These two older persons studied, one with AD and one unaffected, were observed to have increased sex chromosome aneuploidy. This finding was attributed to aging and was not considered to be an effect of AD.     

69,XXY伴严重生长迟缓及眼球突出病例的产前诊断

目的分析孕中期血清筛查数据和胎儿彩色多普勒与染色体异常之间的关系。方法对一孕中期血清产前筛查18三体风险1:10,血清Free-hCGβ异常减低(值为1.29ng/ml即0.08MOM),胎儿系统结构检查提示胎儿小于孕周,头腹围比(1.63)大于正常(1.25),上唇连续性中断延至鼻底的孕妇进行羊膜腔穿刺,抽取羊水进行细胞遗传学检查。结果羊水细胞染色体核型:69,XXY。结论中孕期妇女血清Free-hCGβ异常减低和胎儿头胸围发育不同步、胎儿唇腭裂提示胎儿染色体畸变可能,血清和超声联合筛查有助于染色体疾病的检出。     

广西大厂锡矿区职工外周血淋巴细胞姐妹染色单体交换(SCE)频率、染色体畸变率和微核率的观察

本文分析了38例大厂矿井下矿工、40例井上工作人员和27例非矿区正常人的外周血淋巴细胞SCE频率、染色体畸变率和微核率差异情况,发现井下矿工的SCE频率和染色体畸变率显著高于井上工作人员及非矿区正常人,微核率的差异无显著意义(P>0.05)。结合矿区肺癌流行病学调查结果对比分析,认为井下矿工长期接触的生产性粉尘中可能存在一些致癌物质,导致机体细胞遗传物质受到一定程度损伤。     

180例慢性粒细胞白血病骨髓染色体畸变及意义

目的　研究骨髓染色体畸变与慢性粒细胞白血病 (慢粒 )不同病期的相关性及其临床意义。方法　采取新鲜骨髓 ,进行短期培养 (48小时或 12小时预加秋水仙素培养 )制备染色体标本 ,分析 180例慢粒患者慢性期、加速期、急变期骨髓染色体的变异情况。结果　 180例慢粒患者 ,其中 16 4例Ph染色体阳性 (Ph ) ,占 91 1% ;16例Ph染色体阴性(Ph - ) ,占 8 9%。慢性期 133例Ph ,占总数的 73 9% ;加速期 9例Ph ,占总数 5 0 % ;急变期 2 2例Ph ,占总数12 2 %。 16 4例Ph 慢粒患者中 2 5例 (15 2 % )伴有额外染色体异常 ,其中慢性期占 4 2 7%、加速期占 2 4 %、急变期占8 5 3%。结果表明随着病情的进展 ,Ph 阳性率明显增高 ,其它染色体异常率也明显增高。结论　骨髓染色体畸变与慢粒白血病的病程进展、疾病预后有着十分重要的相关性 ,随着病情的演变 ,骨髓染色体畸变趋于复杂化。进行染色体分析对临床诊断及治疗慢粒具有十分重要的指导意义。     

Genotoxicity of naturally occurring indole compounds: correlation between covalent DNA binding and other genotoxicity tests

3-Methylindole (3MI), melatonin (Mel), serotonin (Ser), and tryptamine (Tryp) were evaluated in vitro for their potential to induce DNA adducts, DNA strand breaks, chromosomal aberrations (Abs), inhibition of DNA synthesis, and mutations. All compounds produced DNA adducts in calf thymus DNA in the presence of rat liver S9. In cultured rat hepatocytes, all produced DNA adducts but none induced DNA strand breaks. In Chinese hamster ovary cells, 3MI and Mel produced DNA adducts, Abs, and inhibition of DNA synthesis with and without S9, except that Mel without S9 did not form adducts. Ser formed DNA adducts, was an equivocal Abs inducer, and suppressed DNA synthesis. Tryp induced neither adducts nor Abs, but did suppress DNA synthesis with S9. Ser and Tryp were less cytotoxic than 3MI and Mel. Mel, Ser, and Tryp failed to induce mutations in Salmonella and E. coli strains with or without S9. 3MI and Mel produced DNA adducts but not mutations in Salmonella TA100 with S9. 3MI and its metabolite indole 3-carbinol also did not induce mutations in a shuttle vector system in human cells. The lack of correlation between DNA adducts and other genotoxicity endpoints for these indole compounds may be due to the higher sensitivity of the (32)P-postlabeling adduct assay or it may indicate that the indole-DNA adducts per se are not mutagenic and are not able to induce strand breaks or alkali-labile lesions. The indole-induced Abs may result from cytotoxicity and suppression of DNA synthesis with minimal if any contribution from DNA adducts.     

Central precocious puberty and abnormal chromosomal patterns

Central precocious puberty (PP) can be caused by chromosomal aberrations. We report three patients presenting with central PP in whom karyotype analysis demonstrated abnormal chromosomal patterns. The first patient was affected by the triple-X syndrome, commonly characterized by premature ovarian failure. The second patient, a girl with inv dup(15)(pter→q12::q12→pter), had a chromosomal aberration involving an imprinted region of the human genome, whose deletion is commonly associated with Prader-Willi syndrome (PWS) and hypogonadotrophic hypogonadism. The third patient was a boy carrying a rare chromosome abnormality, the duplication of chromosome 9 (q22→qter). All patients had mental retardation, which was mild in patient 1, moderate in patient 2, and severe in case 3. They underwent treatment with luteinizing hormone releasing hormone (LHRH) analogs, which were able to stop the progression of the sexual development. We confirm that chromosomal aberrations are an important cause of central PP, and that karyotype analysis in patients with PP and mental retardation, even if mild, is necessary because chromosomal abnormalities can be present.     

69例小儿遗传病分析

本文报告小儿遗传咨询门诊及新生儿科确诊的遗传病:染色体病23例,其中核型异常16例,结构异常7例;常染色体显性遗传病11例,常染色体隐性遗传病28例;性连锁遗传病6例;血红蛋白异常1例,共计69例。常染色体遗传病占55％,染色体异常综合征占33％。常染色体病种类繁多,尽管发病率不高,但危害很大,给诊断带来困难。