Papavassiliou Paulie, York Timothy P, Gursoy Nurcan, Hill Gloria, Nicely Lauren Vanner, Sundaram Usha, McClain Allison, Aggen Steven H, Eaves Lindon, Riley Brien, Jackson-Cook Colleen
Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia 23298-0662, USA.
Am J Med Genet A. 2009 Feb 15;149A(4):573-83. doi: 10.1002/ajmg.a.32729.
Little is known about the pathogenesis of the phenotype in individuals with trisomy 21 mosaicism and Down syndrome. The primary goal of this study was to identify factors contributing to the observed phenotypic variation by evaluating 107 individuals having trisomy 21 mosaicism. To investigate a potential "threshold" effect due to trisomic imbalance, lymphocyte and buccal mucosa nuclei were scored using FISH. Overall, buccal cells showed a significantly higher frequency of trisomy than lymphocytes (P < 0.0001). Using latent class analysis, two phenotypic classes were identified based on the clinical findings of the propositi. Patients from class 1 had significantly fewer traits and a lower percentage of trisomic cells (mean of 37.3% lymphocytes; 34.5% buccal mucosa cells) when compared to those stratified into class 2 (54.0% lymphocytes; 53.4% buccal mucosa cells). Tissue-specific influences were also detected, with buccal mucosa trisomy levels being significantly correlated with IQ (P = 0.0094; both ectodermal derivatives), while congenital heart defects were significantly correlated with lymphocytes (P = 0.0286; both mesodermal embryonic derivatives). In conclusion, allowing for the distinction of two groups, we observed variation in phenotype, associated with the percentage of trisomic cells. We also observed tissue-specific effects on phenotype. The results of this study should enable geneticists and other health care professionals to provide information regarding optimal diagnostic approaches and anticipated clinical outcomes.
对于21三体镶嵌型个体和唐氏综合征患者的表型发病机制,人们了解甚少。本研究的主要目标是通过评估107例21三体镶嵌型个体,来确定导致所观察到的表型变异的因素。为了研究由于三体不平衡导致的潜在“阈值”效应,使用荧光原位杂交(FISH)对淋巴细胞和颊黏膜细胞核进行评分。总体而言,颊细胞的三体频率显著高于淋巴细胞(P < 0.0001)。使用潜在类别分析,根据先证者的临床发现确定了两个表型类别。与分层到第2类的患者相比(淋巴细胞为54.0%;颊黏膜细胞为53.4%),第1类患者的特征明显更少,三体细胞百分比更低(淋巴细胞平均为37.3%;颊黏膜细胞为34.5%)。还检测到了组织特异性影响,颊黏膜三体水平与智商显著相关(P = 0.0094;均为外胚层衍生物),而先天性心脏缺陷与淋巴细胞显著相关(P = 0.0286;均为中胚层胚胎衍生物)。总之,考虑到两组的差异,我们观察到表型变异与三体细胞百分比相关。我们还观察到了对表型的组织特异性影响。本研究结果应能使遗传学家和其他医疗保健专业人员提供有关最佳诊断方法和预期临床结果的信息。