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Bonekey Rep. 2015 Jul 29;4:654. doi: 10.1038/bonekey.2015.21. eCollection 2015.

Missense mutation in the PTEN promoter of a patient with hemifacial hyperplasia.

Author information

1
Childrens Hospital Los Angeles , Los Angeles, CA, USA ; Center for Craniofacial Molecular Biology, University of Southern California , Los Angeles, CA, USA.
2
Clinical Cancer Genetics Program, Human Cancer Genetics Program, Comprehensive Cancer Center, Department of Internal Medicine, The Ohio State University , Columbus, OH, USA.
3
Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health , Bethesda, MD , USA.
4
Childrens Hospital Los Angeles , Los Angeles, CA, USA.
5
Center for Craniofacial Molecular Biology, University of Southern California , Los Angeles, CA, USA.
6
Childrens Hospital Los Angeles , Los Angeles, CA, USA ; Center for Craniofacial Molecular Biology, University of Southern California , Los Angeles, CA, USA ; Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health , Bethesda, MD , USA.

Abstract

The cellular mechanisms involved in the asymmetric facial overgrowth syndrome, hemifacial hyperplasia (HFH), are not well understood. This study was conducted to compare primary cell cultures from hyperplastic and normal HFH bone for cellular and molecular differences. Primary cultures developed from biopsies of a patient with isolated HFH showed a twofold difference in cell size and cell number between hyperplastic and normal bone. Microarray data suggested a 40% suppression of PTEN (phosphatase-tensin homolog) transcripts. Sequencing of the PTEN gene and promoter identified novel C/G missense mutation (position -1053) in the regulatory region of the PTEN promoter. Western blots of downstream pathway components showed an increase in PKBa/Akt1 phosphorylation and TOR (target of rapamcyin) signal. Sirolimus, an inhibitor of TOR, when added to overgrowth cells reversed the cell size, cell number and total protein differences between hyperplastic and normal cells. In cases of facial overgrowth, which involve PTEN/Akt/TOR dysregulation, sirolimus could be used for limiting cell overgrowth.

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