Itoh N, Becroft D M, Reeve A E, Morison I M
Cancer Genetics Laboratory, Department of Biochemistry, University of Otago, Dunedin, New Zealand.
Am J Med Genet. 2000 May 15;92(2):111-6.
"Genetic mosaicism" describes the presence of two or more populations of cells within a single individual that differ in their genomic constitution. Although the occurrence of asymmetric overgrowth in Wiedemann-Beckwith syndrome (WBS) suggests that mosaicism has some role in the WBS phenotype, no direct evidence for this has been published. WBS is a congenital overgrowth syndrome with variable phenotype linked to the imprinted gene cluster on chromosome region 11p15. We have performed a molecular survey of multiple organs and tissues in a case of WBS with a high degree of mosaic paternal 11p15 uniparental disomy (UPD). The organs most severely affected were those with the highest percentage of cells with UPD. In particular there was a striking difference in the degree of mosaicism for 11p15 UPD between the extremely enlarged left adrenal and non-enlarged right adrenal gland. This result indicates that the proportion of paternal 11p15 UPD cells correlates with the tissue phenotype of WBS. Our results suggest that high proportions of abnormal cells result from a combination of stochastic events and cell selection. Mosaicism may explain the variable phenotypes including hemihyperplasia and predisposition to childhood cancers in WBS patients.
“遗传镶嵌现象”指的是单个个体内存在两个或更多基因组构成不同的细胞群体。尽管威德曼-贝克威思综合征（WBS）中不对称过度生长的出现表明镶嵌现象在WBS表型中发挥了一定作用，但尚未有关于此的直接证据发表。WBS是一种先天性过度生长综合征，其可变表型与染色体区域11p15上的印记基因簇相关。我们对一例具有高度镶嵌性父源11p15单亲二体（UPD）的WBS病例的多个器官和组织进行了分子检测。受影响最严重的器官是那些具有UPD细胞百分比最高的器官。特别是，极度增大的左肾上腺和未增大的右肾上腺之间在11p15 UPD的镶嵌程度上存在显著差异。这一结果表明父源11p15 UPD细胞的比例与WBS的组织表型相关。我们的结果表明，高比例的异常细胞是随机事件和细胞选择共同作用的结果。镶嵌现象可能解释了WBS患者包括半侧肥大和儿童癌症易感性在内的可变表型。
