Molecular cytogenetic study on the genetic trait of mitotic checkpoint impairment

(1)早产儿染色单体分离纯合子（PCS: OMIM#176430）特征为马赛克杂色非整倍体，临床表现严重，如发育迟缓、小头畸形、脑发育不全和Wilms肿瘤的发生（Kajii et al., 1998）。来自PCS综合征患者的成纤维细胞显示有丝分裂纺锤体检查点受损（Matsuura等，2001）。通过对10例PCS的临床表现和染色体数据的回顾，包括5例新发现的婴儿，表明PCS的纯合性是一种确定的临床实体，其特征是由于有丝分裂纺锤体检查点的损伤而易患癌症和染色体不稳定综合征（Kajii等）。, 2001)。(2)由于曾有2例PCS婴儿出生，在妊娠15周时进行羊膜穿刺术，所得PCS频率（4.5%）提示胎儿为杂合子。这表明产前诊断两者…更多的异性和纯合子的PCS特征是可能的（Kajii & Asamoto, 2004）。(3)从“PCS”的形态和病理意义的角度阐明了“PCS”一词的定义，特别强调了与“PCD（过早着丝粒分裂：OMIM#212790）”一词的区别，后者只涉及X染色体（Kajii & Ikeuchi, 2004）。(4) PCS细胞的频率是诊断PCS综合征最重要的标志。在PCS性状为纯合或杂合的个体中，37℃低渗处理20分钟的细胞被发现是检测PCS最合适的条件（Ikeuchi et al., 2004）。(5)染色体和DNA多态性标记研究显示，PCS患者的肿瘤在11号染色体上存在单系（父系）二体，提示父亲表达的IGF2等印迹基因的剂量增加主要参与了肿瘤的发展。(6)建立并保存了2例PCS患者的淋巴母细胞样细胞系（LCLs）和成纤维细胞，以及来自杂合载体的大量LCLs。少

(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