Abstract
Tibial hemimelia is a rare, debilitating and often sporadic congenital deficiency. In syndromic cases, mutations of a Sonic hedgehog (SHH) enhancer have been identified. Here we describe an ~5 kb deletion within the SHH repressor GLI3 in two patients with bilateral tibial hemimelia. This deletion results in a truncated GLI3 protein that lacks a DNA-binding domain and cannot repress hedgehog signaling. These findings strengthen the concept that tibial hemimelia arises because of failure to restrict SHH activity to the posterior aspect of the limb bud.
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Acknowledgements
We thank Drs Christian Marshall, Steven Scherer, Sergio Pereira and Chao Lu, and Ms Sylvia Lamoureux from the Centre for Applied Genomics at the Hospital for Sick Children for their valuable advice. This project was supported by the March of Dimes Research Grant 1-FY10-366, Stem Cell Innovation Grant, Hospital for Sick Children and Canadian Institutes of Health Research Operating Grant 137092 (C-cH and SH).
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Deimling, S., Sotiropoulos, C., Lau, K. et al. Tibial hemimelia associated with GLI3 truncation. J Hum Genet 61, 443–446 (2016). https://doi.org/10.1038/jhg.2015.161
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DOI: https://doi.org/10.1038/jhg.2015.161
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