Henry I, Puech A, Riesewijk A, Ahnine L, Mannens M, Beldjord C, Bitoun P, Tournade M F, Landrieu P, Junien C
INSERM U 73, Paris, France.
Eur J Hum Genet. 1993;1(1):19-29. doi: 10.1159/000472384.
Genomic imprinting has been implicated in the aetiology of an overgrowth cancer-prone syndrome, the Wiedemann-Beck-with syndrome (WBS). We have demonstrated uniparental disomy (UPD) for paternal chromosome 11p markers in 5 out of 25 sporadic cases (20%). Delineation of the extent of the disomy region may help in understanding the mechanism and the stage, meiotic or mitotic, of disomy formation in this disease and in associated tumours. Our current studies in WBS patients with seventeen 11p and one 11q markers reveal paternal isodisomy, not heterodisomy, in the five cases. For one case we demonstrate unambiguously that partial isodisomy for 11p and somatic mosaicism for UPD resulted from a post-fertilization event. The restriction of isodisomy to part of 11p in another case, and somatic mosaicism for UPD in three other cases, suggest a mitotic recombinational event that must have occurred after fertilization. Mosaic phenotypes reflect the timing of their origin and the fate of the cells involved, as well as the cell-specific pattern of imprinting. Somatic mosaicism for UPD in four cases may thus explain the incomplete forms of WBS. The association of hemihypertrophy in sporadic WBS and even some cases of isolated hemihypertrophy. This is in agreement with a recent report of paternal isodisomy for 11p markers in a patient with hemihypertrophy, Wilms' tumour and adrenocortical carcinoma. Moreover, the risk of developing a tumour seems higher (50%) for patients with paternal 11p UPD than for WBS patients in general (7.5%).
基因组印记与一种过度生长且易患癌症的综合征——威德曼-贝克维斯综合征（WBS）的病因有关。我们在25例散发病例中的5例（20%）中发现了父源11号染色体短臂标记的单亲二体（UPD）。确定二体区域的范围可能有助于理解该疾病及相关肿瘤中二体形成的机制和阶段（减数分裂或有丝分裂）。我们目前对17个11号染色体短臂和1个11号染色体长臂标记的WBS患者的研究显示，这5例患者为父源同二体，而非异二体。对于其中1例，我们明确证明11号染色体短臂的部分同二体和UPD的体细胞镶嵌现象是受精后事件导致的。在另一例中，同二体局限于11号染色体短臂的一部分，在其他3例中存在UPD的体细胞镶嵌现象，这表明受精后一定发生了有丝分裂重组事件。镶嵌表型反映了它们起源的时间、所涉及细胞的命运以及细胞特异性的印记模式。因此，4例患者中UPD的体细胞镶嵌现象可能解释了WBS的不完全形式。散发型WBS中半身肥大的关联，甚至一些孤立性半身肥大的病例也是如此。这与最近一份关于一名患有半身肥大、肾母细胞瘤和肾上腺皮质癌的患者中父源11号染色体短臂标记同二体的报告一致。此外，父源11号染色体短臂UPD的患者发生肿瘤的风险似乎更高（50%），高于一般WBS患者（7.5%）。
