期刊
AMERICAN JOURNAL OF HUMAN GENETICS
卷 76, 期 4, 页码 652-662出版社
CELL PRESS
DOI: 10.1086/429252
关键词
-
资金
- NICHD NIH HHS [P01 HD039420, P30 HD024064, HD24064, P01 HD39420] Funding Source: Medline
Campomelic dysplasia ( CD) is a semilethal skeletal malformation syndrome with or without XY sex reversal. In addition to the multiple mutations found within the sex-determining region Y - related high-mobility group box gene (SOX9) on 17q24.3, several chromosome anomalies ( translocations, inversions, and deletions) with breakpoints scattered over 1 Mb upstream of SOX9 have been described. Here, we present a balanced translocation, t(4; 17)( q28.3; q24.3), segregating in a family with a mild acampomelic CD with Robin sequence. Both chromosome breakpoints have been identified by fluorescence in situ hybridization and have been sequenced using a somatic cell hybrid. The 17q24.3 breakpoint maps similar to 900 kb upstream of SOX9, which is within the same bacterial artificial chromosome clone as the breakpoints of two other reported patients with mild CD. We also report a prenatal identification of acampomelic CD with male-to-female sex reversal in a fetus with a de novo balanced complex karyotype, 46, XY, t( 4; 7; 8; 17)( 4qter --> 4p15.1:: 17q25.1 --> 17qter --> 7qterr7p15.3:: 4p15.1 --> 4pter; 8pter --> 8q12.1:: 7p15.3 --> 7pter; 17pter --> 17q25.1:: 8q12.1 --> 8qter). Surprisingly, the 17q breakpoint maps similar to 1.3 Mb downstream of SOX9, making this the longest-range position effect found in the field of human genetics and the first report of a patient with CD with the chromosome breakpoint mapping 3' of SOX9. By using the Regulatory Potential score in conjunction with analysis of the rearrangement breakpoints, we identified a candidate upstream cis-regulatory element, SOX9cre1. We provide evidence that this 1.1-kb evolutionarily conserved element and the downstream breakpoint region colocalize with SOX9 in the interphase nucleus, despite being located 1.1 Mb upstream and 1.3 Mb downstream of it, respectively. The potential molecular mechanism responsible for the position effect is discussed.
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