Clarkson Blaise, Pavenski Katerina, Dupuis Lucie, Kennedy Shelley, Meyn Stephen, Nezarati Marjan M, Nie Gloria, Weksberg Rosanna, Withers Stephen, Quercia Nada, Teebi Ahmad S, Teshima Ikuko
Faculty of Medicine, University of Toronto, Toronto, Canada.
Am J Med Genet. 2002 Feb 1;107(4):267-74. doi: 10.1002/ajmg.10240.
The etiology of mental retardation (MR), often presenting as developmental delay in childhood, is unknown in approximately one-half of cases. G-banding is the standard method for investigating those suspected of having a chromosomal etiology; however, detection of structural abnormalities is limited by the size and pattern of the G-bands involved. Rearrangements involving subtelomeric regions have been shown to cause MR and this has generated interest in investigating the prevalence of these rearrangements using telomere-specific probes. In addition, because cryptic interchromosomal rearrangements may not be small or confined to chromosomal ends, spectral karyotyping (SKY) using chromosome-specific painting probes may be of value. We report here a study using these two FISH-based techniques in 50 children with idiopathic MR or developmental delay and normal GTG-banded karyotypes. Our objective was to assess the prevalence of cryptic rearrangements in this population using subtelomeric FISH and SKY. Three rearrangements were detected by subtelomeric FISH: a derivative 5 from a maternal t(5;21); a recombinant 11 from a paternal pericentric inversion; and a 2q deletion that was also present in the mother. Only the derivative 5 was detected by SKY. SKY did not detect any interstitial interchromosomal rearrangement. The prevalence of clinically significant cryptic rearrangements by subtelomeric FISH and SKY was thus 4% (95% confidence interval 0.5-13.7) and 2% (95% CI 0.05-10.7), respectively. This study supports the view that G-banding does not detect all clinically significant chromosomal abnormalities and that subtelomeric FISH and SKY can detect some of these abnormalities.
智力迟钝（MR）通常表现为儿童期发育迟缓，约半数病例的病因不明。G显带是调查怀疑有染色体病因者的标准方法；然而，结构异常的检测受所涉及G带的大小和模式限制。已表明涉及亚端粒区域的重排可导致MR，这引起了人们对使用端粒特异性探针研究这些重排发生率的兴趣。此外，由于隐匿的染色体间重排可能不小或不限于染色体末端，使用染色体特异性涂染探针的光谱核型分析（SKY）可能有价值。我们在此报告一项针对50名特发性MR或发育迟缓且GTG带型核型正常的儿童使用这两种基于荧光原位杂交（FISH）技术的研究。我们的目的是使用亚端粒FISH和SKY评估该人群中隐匿重排的发生率。通过亚端粒FISH检测到3种重排：来自母亲t(5;21)的衍生5号染色体；来自父亲臂间倒位的重组11号染色体；以及母亲也存在的2号染色体q臂缺失。SKY仅检测到衍生5号染色体。SKY未检测到任何染色体间的间质重排。因此，通过亚端粒FISH和SKY检测到的具有临床意义的隐匿重排发生率分别为4%（95%置信区间0.5 - 13.7）和2%（95%CI 0.05 - 10.7）。这项研究支持以下观点，即G显带不能检测出所有具有临床意义的染色体异常，而亚端粒FISH和SKY可以检测出其中一些异常。
