Journal
EUROPEAN JOURNAL OF HUMAN GENETICS
Volume 18, Issue 6, Pages 733-736Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ejhg.2009.225
Keywords
preaxial polydactyly; triphalangeal thumb; point mutation; SHH regulatory sequence, regulatory element
Funding
- Higher Education Commission of Pakistan
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A cis-regulatory sequence also known as zone of polarizing activity (ZPA) regulatory sequence (ZRS) located in intron 5 of LMBR1 is essential for expression of sonic hedgehog (SHH) in the developing posterior limb bud mesenchyme. Even though many point mutations causing preaxial duplication defects have been reported in ZRS, the underlying regulatory mechanism is still unknown. In this study, we analyzed the effect on transcription factor binding of a novel ZRS point mutation (463T>G) in a Pakistani family with preaxial polydactyly and triphalangeal thumb. Electrophoretical mobility shift assay demonstrated a marked difference between wild-type and the mutant probe, which uniquely bound one or several transcription factors extracted from Caco-2 cells. This finding supports a model in which ectopic anterior SHH expression in the developing limb results from abnormal binding of one or more transcription factors to the mutant sequence. European Journal of Human Genetics (2010) 18, 733-736; doi: 10.1038/ejhg.2009.225; published online 13 January 2010
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