Department of Pediatric Dentistry, Craniofacial Genetics Laboratory, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.
Eur J Hum Genet. 2010 Dec;18(12):1310-4. doi: 10.1038/ejhg.2010.116. Epub 2010 Jul 21.
Mesomelic dysplasia Kantaputra type (MDK) is characterized by marked mesomelic shortening of the upper and lower limbs originally described in a Thai family. To identify the cause of MDK, we performed array CGH and identified two microduplications on chromosome 2 (2q31.1-q31.2) encompassing ∼481 and 507 kb, separated by a segment of normal copy number. The more centromeric duplication encompasses the entire HOXD cluster, as well as the neighboring genes EVX2 and MTX2. The breakpoints of the duplication localize to the same region as the previously identified inversion of the mouse mutant ulnaless (Ul), which has a similar phenotype as MDK. We propose that MDK is caused by duplications that modify the topography of the locus and as such result in deregulation of HOXD gene expression.
Kantaputra 型中胚层发育不良(MDK)的特征是上肢和下肢明显的中胚层缩短,最初在一个泰国家庭中描述。为了确定 MDK 的原因,我们进行了 array CGH 分析,发现 2 号染色体(2q31.1-q31.2)上有两个微重复,大小分别约为 481 和 507 kb,中间有一段正常的拷贝数。更靠近着丝粒的重复包含整个 HOXD 簇以及相邻的 EVX2 和 MTX2 基因。重复的断点与先前鉴定的 mouse mutant ulnaless(Ul)的倒位位于同一区域,其表型与 MDK 相似。我们提出 MDK 是由重复引起的,这些重复改变了基因座的拓扑结构,从而导致 HOXD 基因表达的失调。