期刊
HUMAN MUTATION
卷 30, 期 11, 页码 1535-1542出版社
WILEY
DOI: 10.1002/humu.21095
关键词
SMC1A; CdLS; X-linked; expression
资金
- CdLS Foundation Fellowship
- National Institute of Child Health and Human Development [PO1 HDO52860, R21 HD050538, K08 HD055488]
Cornelia de Lange Syndrome (CdLS) is a dominantly inherited heterogeneous genetic disorder with multisystem abnormalities. Sixty percent of probands with CdLS have heterozygous mutations in the Nipped-B-like (NIPBL) gene, 5% have mutations in the SMC1A gene, and one proband was found to have a mutation in the SMC3 gene. Cohesin is a multisubunit complex consisting of a SMC1A and SMC3 heterodimer and two non-SMC subunits. SMC1A is located on the human X chromosome and is reported to escape X inactivation. Twenty-nine unrelated CdLS probands with 21 unique SMC1A mutations have been identified including seven males. All mutations identified to date are either missense or small deletions, with all presumably preserving the protein open reading frame. Both wild,type and mutant alleles are expressed. Females quantitatively express twice the amount of SMC1A mRNA compared to males. The transcriptional profiling of 23 selected genes is different in SMC1A mutant probands, controls, and NIPBL mutant probands. These results suggest that mechanistically SMC1A-related CdLS is not due to altered levels of the SMC1A transcript, but rather that the mutant proteins maintain a residual function in males and enact a dominant negative effect in females. Hum Mutat 30:1535-1542, 2009. (C) 2009 Wiley-Liss, Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据