Domínguez M G, Barros-Núñez P, González-Ramos I A, Rivera H
Doctorado en Genética Humana, CIBO-IMSS and CUCS-U de G, Guadalajara Jal, México.
Genet Couns. 2010;21(4):411-22.
A 13-month-old boy with normal development and growth failure of prenatal onset but no other physical stigmata had a 46,XY,r(4)(p1 6.3q35).ish (4psubtel-, WHS1+, 4qsubtel+, pantel-) de novo karyotype. The analysis of 50-106 metaphases from each of four lymphocyte cultures (three of 72 h including one without colchicine and one of 96 h) revealed a dynamic mosaicism in 22-36% of cells. We did not observe a normal cell line. Hypoploidies (excluding ring losses) were observed in 2-7% of metaphases from colchicine-arrested cultures whereas tetraploidies were observed in 2-12% of metaphases from all four lymphocyte cultures. Further FISH studies were carried out on interphase nuclei from uncultured buccal cells and lymphocytes using two alphoid (CEP 1 and 9), a dual CEP X/SRY, and (in the former only) a subtel 4p probes. We scored 70-131 nuclei per assay and found apparent heteroploidies in approximately 1-47% of cells for CEP 1, CEP 9, subtel 4p, and SRY but not for CEP X. The patient's phenotype was typical of the ring syndrome and comparable to 9/37 previous r(4) cases. Moreover, all 38 patients were alive at the time of reporting and none has developed cancer. The 2-7% rate of hypodiploid cells in colchicine-arrested cultures and the approximately 1-47% rate of apparent heteroploidies in nuclei of uncultured cells evoke the in vitro and in vivo findings in patients with mosaic variegated aneuploidy (MVA). We conclude that our observation highlights the clinical and cytogenetical overlapping between the ring syndrome and the MVA syndrome; the crucial difference is the high risk of cancer related to BUB1B mutations in the latter.
一名13个月大的男孩，发育正常，但产前开始生长发育迟缓，无其他身体特征，其核型为46,XY,r(4)(p16.3q35)。ish(4psubtel-,WHS1+,4qsubtel+,pantel-)新发核型。对来自四种淋巴细胞培养物（三种72小时，包括一种未加秋水仙碱的，一种是加了秋水仙碱的96小时培养物）的50 - 106个中期细胞进行分析，发现22% - 36%的细胞存在动态镶嵌现象。我们未观察到正常细胞系。在秋水仙碱阻断培养的中期细胞中，2% - 7%观察到亚二倍体（不包括环状染色体丢失），而在所有四种淋巴细胞培养物的中期细胞中，2% - 12%观察到四倍体。使用两种α卫星（CEP 1和9）、一种CEP X/SRY双色探针以及（仅在前一种情况下）一种4p端粒探针，对未培养的颊细胞和淋巴细胞的间期核进行了进一步的荧光原位杂交（FISH）研究。每次检测我们对70 - 131个核进行评分，发现对于CEP 1、CEP 9、4p端粒和SRY，约1% - 47%的细胞存在明显的异倍体，但对于CEP X未发现。患者的表型是典型的环状染色体综合征，与之前37例r(4)病例中的9例相似。此外，在报告时所有38例患者均存活，且无一例发生癌症。秋水仙碱阻断培养中2% - 7%的亚二倍体细胞率以及未培养细胞的核中约1% - 47%的明显异倍体率，让人联想到镶嵌型杂合性非整倍体（MVA）患者的体外和体内研究结果。我们得出结论，我们的观察结果突出了环状染色体综合征和MVA综合征在临床和细胞遗传学上的重叠；关键区别在于后者与BUB1B突变相关的癌症高风险。
