ヤマモト　トシユキ   Yamamoto Toshiyuki   山本　俊至    所属   医学部 医学科（東京女子医科大学病院）    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読なし
表題	Tandem configurations of variably duplicated segments of 22q11.2 confirmed by fiber-FISH analysis.
掲載誌名	正式名：Journal of Human Genetics
巻・号・頁	56(11),pp.810-812
著者・共著者	Keiko Shimojima, Nobuhiko Okamoto, Tetsuya Inazu, Toshiyuki Yamamoto
発行年月	2011/11
概要	22q11.2 duplication syndrome has recently been established as a new syndrome manifesting broad clinical phenotypes including mental retardation. It is reciprocal to DiGeorge (DGS)/velo-cardio-facial syndrome (VCFS), in which the same portion of the chromosome is hemizygously deleted. Deletions and duplications of the 22q11.2 region are facilitated by the low-copy repeats (LCRs) flanking this region. In this study, we aimed to identify the directions of the duplicated segments of 22q11.2 to better understand the mechanism of chromosomal duplication. To achieve this aim, we accumulated samples from four patients with 22q11.2 duplications. One of the patients had an atypically small (741 kb) duplication of 22q11.2. The centromeric end of the breakpoint was on LCR22A, but the telomeric end was between LCR22A and B. Therefore, the duplicated segment did not include T-box 1 gene (TBX1), the gene primarily responsible for the DGS/VCFS. As this duplication was shared by the patient's healthy mother, this appears to be a benign copy-number variation rather than a disease-causing alteration. The other three patients showed 3.0 or 4.0 Mb duplications flanked by LCRs. The directions of the duplicated segments were investigated by fiber-fluorescence in situ hybridization analysis. All samples showed tandem configurations. These results support the hypothesized mechanism of non-allelic homologous recombination with flanking LCRs and add additional evidence that many interstitial duplications are aligned as tandem configurations.
DOI	10.1038