Abstract
Mutations in some exons of the RET proto-oncogene were recently observed in Hirschsprung patients. Using DNA polymorphisms and single-strand conformation polymorphism analysis for the whole coding sequence of the RET proto-oncogene, 82 unrelated Hirschsprung patients were screened systematically. A total of 4 complete deletions of RET and 12 point mutations were identified, each present in no more than one patient and distributed along the whole gene. De novo mutations could be documented in 4 patients. Southern blot and fluorescence in situ hybridization analysis carried out in a restricted number of patients did not reveal any deletion of RET. The low efficiency in detecting mutations of RET in Hirschsprung patients (20%) may originate mainly from genetic heterogeneity.
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Acknowledgements
We thank Dr. M. Takahashi for a RET cDNA probe, Francesco Caroli, Donatella Concedi and Monica Scaranari for their technical help, Dr. Monica Bozzano and Dr. Paola Ghisellini for participating in part of this work, which was supported by the AIRC, the Italian Telethon, PF ‘Ingegneria Genetica’, the Italian CNR (Progetto Finalizzato Ingegneria Genetica), the Italian Ministry of Health and the EU (PL910027). Y.L. and B.P. are supported by fellowships from Telethon and from Associazione Italiana per la Ricerca sul Cancro, respectively. The following clinicians have contributed blood from patients included in this study in whom we could not identify any RET mutations: Prof. S. Auricchio (Naples, Italy), Dr. I. Baric (Zagreb, Croatia), Prof. A. Schinzel (Zürich, Switzerland), Dr. J.M. Casasa (Barcelona, Spain), Dr. C. Monteiro (Lisbon, Portugal), Dr. L. Cutrone (Campobasso, Italy), Dr. I. van der Burgt (Nijmegen, The Netherlands), Dr. Albert Szent (Szeged, Hungary), Dr. M. Rady (Cairo, Egypt) and Dr. L. Van Maldergem (Loverval, Belgium).
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Yin, L., Barone, V., Seri, M. et al. Heterogeneity and Low Detection Rate of RET Mutations in Hirschsprung Disease. Eur J Hum Genet 2, 272–280 (1994). https://doi.org/10.1159/000472371
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DOI: https://doi.org/10.1159/000472371
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