Germline mutations in HRAS proto-oncogene cause Costello syndrome (original) (raw)

Nature Genetics volume 37, pages 1038–1040 (2005)Cite this article

Abstract

Costello syndrome is a multiple congenital anomaly and mental retardation syndrome characterized by coarse face, loose skin, cardiomyopathy and predisposition to tumors. We identified four heterozygous de novo mutations of HRAS in 12 of 13 affected individuals, all of which were previously reported as somatic and oncogenic mutations in various tumors. Our observations suggest that germline mutations in HRAS perturb human development and increase susceptibility to tumors.

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Figure 1: HRAS mutations in Costello syndrome.

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Acknowledgements

We thank the individuals and their families for participating in this study; the doctors for referring the cases; the “Diagnosi PrePostnatale Malattie Metaboliche” Laboratory (G. Gaslini Institute) for providing us with specimens from the “Cell line and DNA bank from patients affected by genetic diseases” Biobank, supported by TELETHON grants; and the Japan Health Sciences Foundation for providing us with control fibroblasts (TIG118-120) from Health Science Research Resources Bank. This work was supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan to Y.A.

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Authors and Affiliations

  1. Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Sendai, 980-8574, Japan
    Yoko Aoki, Tetsuya Niihori, Kumi Kato, Yoichi Suzuki, Shigeo Kure & Yoichi Matsubara
  2. Division of Medical Genetics, Nagano Children's Hospital, Nagano, Japan
    Hiroshi Kawame
  3. Division of Medical Genetics, Kanagawa Children's Medical Center, Yokohama, Japan
    Kenji Kurosawa
  4. Division of Medical Genetics, Saitama Children's Medical Center, Saitama, Japan
    Hirofumi Ohashi
  5. Division of Pathology, Kanagawa Children's Medical Center, Yokohama, Japan
    Yukichi Tanaka
  6. Laboratorio Diagnosi Pre-Postnatale Malattie Metaboliche, IRCCS G. Gaslini, Genova, Italy
    Mirella Filocamo
  7. Tohoku University 21st Century COE Program “Comprehensive Research and Education Center for Planning of Drug Development and Clinical Evaluation,”, Sendai, Japan
    Kumi Kato & Yoichi Matsubara

Authors

  1. Yoko Aoki
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  2. Tetsuya Niihori
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  3. Hiroshi Kawame
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  4. Kenji Kurosawa
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  5. Hirofumi Ohashi
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  6. Yukichi Tanaka
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  7. Mirella Filocamo
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  8. Kumi Kato
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  9. Yoichi Suzuki
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  10. Shigeo Kure
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  11. Yoichi Matsubara
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Correspondence toYoko Aoki.

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Aoki, Y., Niihori, T., Kawame, H. et al. Germline mutations in HRAS proto-oncogene cause Costello syndrome.Nat Genet 37, 1038–1040 (2005). https://doi.org/10.1038/ng1641

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