Abstract
Epigenetic defects in the imprinted GNAS cluster are associated with pseudohypoparathyroidism type Ib. In two kindreds with this disorder, we now report deletions that remove the differentially methylated region encompassing exon NESP55 and exons 3 and 4 of the antisense transcript. When inherited from a female, either deletion abolishes all maternal GNAS imprints and derepresses maternally silenced transcripts, suggesting that the deleted region contains a cis-acting element that controls imprinting of the maternal GNAS allele.
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Acknowledgements
We thank H.M. Kronenberg and J.T. Lee for critically reviewing the manuscript. This work was funded, in part, by separate grants from National Institute of Diabetes and Digestive and Kidney Diseases (to M.B. and H.J.).
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Supplementary information
Supplementary Fig. 1
The two AD-PHP-Ib kindreds with the NESP55 DMR deletion. (PDF 93 kb)
Supplementary Fig. 2
A novel AS RT-PCR product containing a previously non-described exon. (PDF 115 kb)
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Bastepe, M., Fröhlich, L., Linglart, A. et al. Deletion of the NESP55 differentially methylated region causes loss of maternal GNAS imprints and pseudohypoparathyroidism type Ib. Nat Genet 37, 25–27 (2005). https://doi.org/10.1038/ng1487
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DOI: https://doi.org/10.1038/ng1487
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