Abstract
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.
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Acknowledgements
We thank the family for participating in this study. This work was supported by grants from the Deutsche Forschungsgemeinschaft to SM and EK, and the Thailand Research Fund (TRF) to PK.
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Kantaputra, P., Klopocki, E., Hennig, B. et al. Mesomelic dysplasia Kantaputra type is associated with duplications of the HOXD locus on chromosome 2q. Eur J Hum Genet 18, 1310–1314 (2010). https://doi.org/10.1038/ejhg.2010.116
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DOI: https://doi.org/10.1038/ejhg.2010.116
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