AI Article Synopsis
- The study investigates Beckwith-Wiedemann syndrome (BWS) and Wilms' tumor in families, focusing on gene expression control in the 11p15 chromosome region.
- A specific 2.2-kbp microdeletion in the H19/IGF2-imprinting center was identified, affecting a key chromatin protein (CTCF) thought to contribute to BWS and Wilms' tumor development.
- Maternal inheritance of the deletion leads to increased IGF2 mRNA expression, but a second genetic change in one individual (a duplication of 11p15) further elevates IGF2 levels, suggesting both genetic alterations together are critical for BWS occurrence.
Article Abstract
We have analyzed several cases of Beckwith-Wiedemann syndrome (BWS) with Wilms' tumor in a familial setting, which give insight into the complex controls of imprinting and gene expression in the chromosome 11p15 region. We describe a 2.2-kbp microdeletion in the H19/insulin-like growth factor 2 (IGF2)-imprinting center eliminating three target sites of the chromatin insulator protein CTCF that we believe here is necessary, but not sufficient, to cause BWS and Wilms' tumor. Maternal inheritance of the deletion is associated with IGF2 loss of imprinting and up-regulation of IGF2 mRNA. However, in at least one affected family member a second genetic lesion (a duplication of maternal 11p15) was identified and accompanied by a further increase in IGF2 mRNA levels 35-fold higher than control values. Our results suggest that the combined effects of the H19/IGF2-imprinting center microdeletion and 11p15 chromosome duplication were necessary for manifestation of BWS.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC554791 | PMC |
| http://dx.doi.org/10.1073/pnas.0500037102 | DOI Listing |
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