Molecular cytogenetic study on the genetic trait of mitotic checkpoint impairment

有丝分裂检查点障碍遗传性状的分子细胞遗传学研究

基本信息

批准号：
13672374
负责人：
IKEUCHI Tatsuro
金额：
$ 2.3万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

项目摘要

(1) Infants homozygous for the premature chromatid separation (PCS : OMIM#176430) trait are characterized by mosaic variegated aneuploidy and severe clinical manifestations such as growth retardation, microcephaly, brain hypoplasia, and development of Wilms tumor (Kajii et al., 1998). Fifbroblasts from patients with PCS syndrome show impairment of the mitotic spindle checkpoint (Matsuura et al., 2001). A review of the clinical manifestations and chromosomal data in 10 cases of PCS including the 5 newly detected infants showed that homozygosity for the PCS trait is an established clinical entity characterized by susceptibility to cancer and chromosomal instability syndrome due to impairment of mitotic spindle checkpoint (Kajii et all., 2001).(2) Amniocentesis was performed at 15 wks of pregnancy because of previous deliveries of two PCS infants, and the obtained PCS frequencies (4.5%) suggested that the fetus was heterozygous for the trait. This indicates that prenatal diagnosis of both … More hetero-and homozygosity for the PCS trait is possible (Kajii & Asamoto, 2004).(3) Definition of the term "PCS" was clarified from the standpoints of its configuration and pathological significance, with special emphasis on the diffenence from the term "PCD (premature centromere division : OMIM#212790)" which involves the X chromosome exclusively (Kajii & Ikeuchi, 2004).(4) The frequency of cells in PCS is the most important hallmark for diagnosis of PCS syndrome. Hypotonic treatment of cells at 37℃ for 20 min was found to be most suitable among the conditions tested for the detection of PCS in individuals with the homozygous or heterozygous for the PCS trait (Ikeuchi et al., 2004).(5) Chromomal and DNA polymorphic marker studies revealed that the tumors developing in PCS patients had uniparental (paternal) disomy for chromosome 11, suggesting that the increased dosage of imprinted genes such as paternally expressed IGF2 was primarily involved in tumor development.(6) Lymphoblastoid cell lines (LCLs) and fibroblasts derived from the two PCS patients and a number of LCLs from heterozygous carriers were established and stored. Less

（1）纯合染色单体分离（PCS：OMIM＃176430）特征的婴儿的特征是镶嵌性杂色的非整倍性和严重的临床表现，例如生长迟缓，微头脑脑，脑脑下型，脑下脑下浮肿和Wilms肿瘤的发育（Kajii et al。，1998年）。来自PCS综合征患者的FIFBROBLASTS显示出有丝分裂纺锤体检查点的损害（Matsuura等，2001）。 A review of the clinical manifestations and chromosomal data in 10 cases of PCS including the 5 newly detected infants showed that homozygosity for the PCS trait is an established clinical entity characterised by susceptibility to cancer and chromosomal instability syndrome due to impairment of mitotic spindle checkpoint (Kajii et all., 2001).(2) Amniocentesis was performed at 15 wks of pregnancy由于先前的两个PC婴儿，并且获得的PC频率（4.5％）表明该性状是杂合的。这表明两者的产前诊断……对PCS性状的更异性和纯合性是可能的（Kajii＆Asamoto，2004年）。（3）“ PCS”一词的定义是从配置和病理学意义的角度阐明的，与该期限的差异有关。染色体专门（Kajii＆Ikeuchi，2004）。（4）PC中细胞的频率是PC综合征诊断的最重要标志。 Hypotonic treatment of cells at 37℃ for 20 min was found to be most suitable among the conditions tested for the detection of PCS in individuals with the homozygous or heterozygous for the PCS trait (Ikeuchi et al., 2004).(5) Chromomal and DNA polymorphic marker studies revealed that the tumors developing in PCS patients had uniparental (paternal) disomy for chromosome 11, suggesting that印迹基因（例如图案表达的IGF2）的剂量增加主要参与肿瘤的发育。（6）淋巴母细胞细胞系（LCLS）和来自两名PCS患者的成纤维细胞以及来自杂合载体的许多LCL的成纤维细胞。较少的