Microdeletion of LIT1 in familial Beckwith-Wiedemann syndrome
Microdeletion of LIT1 in familial Beckwith-Wiedemann syndrome
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DOI：
10.1086/425343
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发表时间：
2004-11-01
影响因子：
9.8
通讯作者：
Feinberg, AP
中科院分区：
文献类型：
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作者：
Niemitz, EL;DeBaun, MR;Feinberg, AP
Beckwith-Wiedemann综合征(BWS)导致产前过度生长、中线腹壁缺陷、巨舌症和胚胎肿瘤，是了解基因组印记、人类发育和癌症之间关系的模型。原因是异质性的，涉及11p15上的多个基因，包括罕见的p57突变(KIP2)或11p15上两个印记基因结构域中的一个印记丢失：接近p57的LIT1(KIP2)或H19/IGF2。与Prader-Willi和Angelman综合征不同，目前还没有发现染色体缺失。在这里，我们报告了一个包括整个LIT1基因的微缺失，从遗传学上证实了该基因区域在BWS中的重要性。当母系遗传时，该缺失导致BWS的p57(KIP2)沉默，表明缺失了对p57(KIP2)表达调节重要的元件。当从父系遗传时，没有表型，这表明LIT1 RNA本身对人类的正常发育不是必需的。
Beckwith-Wiedemann syndrome (BWS), which causes prenatal overgrowth, midline abdominal wall defects, macroglossia, and embryonal tumors, is a model for understanding the relationship between genomic imprinting, human development, and cancer. The causes are heterogeneous, involving multiple genes on 11p15 and including infrequent mutation of p57(KIP2) or loss of imprinting of either of two imprinted gene domains on 11p15: LIT1, which is near p57(KIP2), or H19/IGF2. Unlike Prader-Willi and Angelman syndromes, no chromosomal deletions have yet been identified. Here we report a microdeletion including the entire LIT1 gene, providing genetic confirmation of the importance of this gene region in BWS. When inherited maternally, the deletion causes BWS with silencing of p57(KIP2), indicating deletion of an element important for the regulation of p57(KIP2) expression. When inherited paternally, there is no phenotype, suggesting that the LIT1 RNA itself is not necessary for normal development in humans.