Flejter W L, Issa B, Sullivan B A, Carey J C, Brothman A R
Department of Pediatrics, University of Utah, Salt Lake City 84132, USA.
Am J Med Genet. 1998 Jan 6;75(1):45-51.
Cytogenetic studies of 2 sisters with mild microcephaly, growth deficiency, and mild errors of morphogenesis demonstrated a unique combination of multiple trisomies, most often involving chromosomes 8 and 18 either together as sole trisomies or in combination with other chromosomes. Since neither sib has phenotypic anomalies associated with trisomy 8 or 18 mosaicism, the trisomies likely did not occur during embryogenesis, but later possibly due to a predisposition for mitotic instability. To determine if the observed chromosome instability may be related to centromere function, metaphase cells were characterized by immunofluorescence of the centromere protein, CENP-E. Hybridization of CENP-E antibodies, in combination with in situ hybridization of a chromosome 8 or 18 alpha-satellite probe, showed hybridization to chromosomes 8 and 18 in both normal and aneuploid cells from each patient. These data indicate that the chromosomes in each child contain functional and active centromeres. The clinical and cytogenetic findings in these 2 individuals are compared with 7 other previously reported individuals, each of whom have similar findings. Together, these studies support the notion that a recessive mitotic mutant may be responsible for the chromosomal mosaicism and for the resulting clinical phenotype.
对两名患有轻度小头畸形、生长发育迟缓以及轻度形态发生异常的姐妹进行的细胞遗传学研究显示，存在多种三体性的独特组合，最常见的是8号和18号染色体一起作为唯一的三体，或者与其他染色体组合。由于这两名姐妹均无与8号或18号染色体嵌合体相关的表型异常，这些三体性可能并非在胚胎发生过程中出现，而是后来可能由于有丝分裂不稳定性的倾向所致。为了确定观察到的染色体不稳定性是否可能与着丝粒功能有关，通过着丝粒蛋白CENP - E的免疫荧光对中期细胞进行了表征。CENP - E抗体的杂交，结合8号或18号染色体α - 卫星探针的原位杂交，显示在每位患者的正常细胞和非整倍体细胞中均与8号和18号染色体杂交。这些数据表明每个孩子的染色体都包含功能性和活性着丝粒。将这两名个体的临床和细胞遗传学发现与其他7名先前报道的个体进行了比较，他们每个人都有类似的发现。总之，这些研究支持这样一种观点，即隐性有丝分裂突变体可能是染色体嵌合体以及由此产生的临床表型的原因。
