人类染色体区域11p15.3 - pter的亲本印记与贝克威思-维德曼综合征及多种人类肿瘤形成有关。

Parental imprinting of human chromosome region 11p15.3-pter involved in the Beckwith-Wiedemann syndrome and various human neoplasia.

作者信息

Mannens M, Hoovers J M, Redeker E, Verjaal M, Feinberg A P, Little P, Boavida M, Coad N, Steenman M, Bliek J

机构信息

Institute of Human Genetics, University of Amsterdam, The Netherlands.

出版信息

Eur J Hum Genet. 1994;2(1):3-23. doi: 10.1159/000472337.

DOI:10.1159/000472337

PMID:7913866

Abstract

Cytogenetic and DNA analyses of patients with the Beckwith-Wiedemann syndrome (BWS) enabled us to refine the localization of the syndrome at 11p15.3-pter to two distinct regions. One chromosome region (BWSCR1) is near the insulin (INS) and insulin-like growth factor 2 (IGF2) genes. The other region (BWSCR2) is more proximal near two sequences with zinc-binding finger motifs and a number of known and putative genes. This latter region, at least, seems to be associated with the development of childhood tumors. Our results strongly support the proposed involvement of parental imprinting in the etiology of BWS since all balanced chromosomal abnormalities in these patients were maternally transmitted while the mothers were phenotypically normal. We demonstrate that such an autosomal balanced rearrangement can lead to a specific maternal hypomethylation of the INS/IGF2 genes localized distal to the breakpoint. This underlines the role of these genes in the etiology of the syndrome.

摘要

对贝克威思-维德曼综合征（BWS）患者进行的细胞遗传学和DNA分析，使我们能够将该综合征的定位在11p15.3 - pter区域内细化为两个不同的区域。一个染色体区域（BWSCR1）靠近胰岛素（INS）和胰岛素样生长因子2（IGF2）基因。另一个区域（BWSCR2）更靠近近端，有两个具有锌结合指基序的序列以及一些已知和推测的基因。至少后一个区域似乎与儿童肿瘤的发生有关。我们的结果有力地支持了关于亲本印记参与BWS病因的提议，因为这些患者所有的平衡染色体异常都是由母亲遗传而来，而母亲的表型是正常的。我们证明，这种常染色体平衡重排可导致位于断点远端的INS/IGF2基因发生特定的母体低甲基化。这突出了这些基因在该综合征病因中的作用。