期刊
HUMAN MUTATION
卷 30, 期 12, 页码 1667-1675出版社
WILEY
DOI: 10.1002/humu.21117
关键词
Ellis-van Creveld syndrome; Weyer acrodental dysostosis; EVC; EVC2; Hedgehog signaling
资金
- Spanish Ministry of Science and Innovation [SAF-62291]
- Ramon Areces Foundation
- European Union [LSHM-CT-2007-03741]
Autosomal recessive Ellis-van Creveld syndrome and autosomal dominant Weyer acrodental dysostosis are allelic conditions caused by mutations in EVC or EVC2. We performed a mutation screening study in 36 EvC cases and 3 cases of Weyer acrodental dysostosis, and identified pathogenic changes either in EVC or in EVC2 in all cases. We detected 40 independent EVC/EVC2 mutations of which 29 were novel changes in Ellis,van Creveld cases and 2 were novel mutations identified in Weyer pedigrees. Of interest one EvC patient had a T>G nucleotide substitution in intron 7 of EVC (c.940-150T>G), which creates a new donor splice site and results in the inclusion of a new exon. The T>G substitution is at nucleotide +5 of the novel 5' splice site. The three Weyer mutations occurred in the final exon of EVC2 (exon 22), suggesting that specific residues encoded by this exon are a key part of the protein. Using murine versions of EVC2 exon 22 mutations we demonstrate that the expression of a Weyer variant, but not the expression of a truncated protein that mimics an Ellis-van Creveld syndrome mutation, impairs Hedgehog signal transduction in NIH 3T3 cells in keeping with its dominant effect. Hum Mutat 30:1667-1675, 2009. (C) 2009 Wiley-Liss, Inc.
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