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No evidence of PEG1/MEST gene mutations in Silver‐Russell syndrome patients |
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| Authors: | Shin Kobayashi Hiraku Uemura Takashi Kohda Toshiro Nagai Yasutsugu Chinen Kenji Naritomi Ei‐ichi Kinoshita Hirofumi Ohashi Kiyoshi Imaizumi Masato Tsukahara Yoshitsugu Sugio Hidefumi Tonoki Tatsuya Kishino Toshiaki Tanaka Masao Yamada Osamu Tsutsumi Norio Niikawa Tomoko Kaneko‐Ishino Fumitoshi Ishino |
| Affiliation: | 1. Gene Research Center, Tokyo Institute of Technology, Yokohama, Japan;2. CREST, Japan Science and Technology Corporation (JST), Saitama, Japan;3. Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan;4. Department of Pediatrics, Dokkyo University School of Medicine Koshigaya Hospital, Saitama, Japan;5. Department of Pediatrics, University of the Ryukyus School of Medicine, Okinawa, Japan;6. Department of Medical Genetics, Okinawa‐Asia Research Center for Medical Science, University of the Ryukyus School of Medicine, Okinawa, Japan;7. Department of Pediatrics, Nagasaki University School of Medicine, Nagasaki, Japan;8. Division of Medical Genetics, Saitama Children's Medical Center, Saitama, Japan;9. Division of Medical Genetics, Kanagawa Children's Medical Center, Kanagawa, Japan;10. Faculty of Health Sciences, Yamaguchi University, Yamaguchi, Japan;11. Department of Pediatrics, Ogori Daiichi General Hospital, Yamaguchi, Japan;12. Department of Pediatrics, Hokkaido University School of Medicine, Hokkaido, Japan;13. Department of Human Genetics, Nagasaki University School of Medicine, Nagasaki, Japan;14. Department of Endocrinology and Metabolism, National Children's Medical Research Center, Tokyo, Japan;15. Department of Genetics, National Children's Medical Research Center, Tokyo, Japan;16. Department of Obstetrics and Gynecology, Mejirodai Campus, Faculty of Medicine, The University of Tokyo, Tokyo, Japan;17. Tokai University, School of Health Sciences, Kanagawa, Japan |
| Abstract: | Silver‐Russell syndrome (SRS) is characterized by prenatal and postnatal growth retardation with morphologic anomalies. Maternal uniparental disomy 7 has been reported in some SRS patients. PEG1/MEST is an imprinted gene on chromosome 7q32 that is expressed only from the paternal allele and is a candidate gene for SRS. To clarify its biological function and role in SRS, we screened PEG1/MEST abnormalities in 15 SRS patients from various standpoints. In the lymphocytes of SRS patients, no aberrant expression patterns of two splice variants (α and β) of PEG1/MEST were detected when they were compared with normal samples. Direct sequence analysis failed to detect any mutations in the PEG1/MEST α coding region, and there were no significant mutations in the 5′‐flanking upstream region containing the predicted promoter and the highly conserved human/mouse genomic region. Differential methylation patterns of the CpG island for PEG1/MEST α were normally maintained and resulted in the same pattern as in the normal control, suggesting that there was no loss of imprinting. These findings suggest that PEG1/MEST can be excluded as a major determinant of SRS. © 2001 Wiley‐Liss, Inc. |
| Keywords: | genomic imprinting PEG1/MEST Silver‐Russell syndrome growth retardation |