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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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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Supplementary information
Supplementary Fig. 1
Photographs of patients' faces and histopathology of cardiomyopathy and ganglioneuroblastoma. (PDF 925 kb)
Supplementary Fig. 2
Mutation analysis of 12 affected individuals and their families. (PDF 1360 kb)
Supplementary Table 1
Clinical data of Japanese individuals with Costello syndrome. (PDF 116 kb)
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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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DOI: https://doi.org/10.1038/ng1641
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