Loss of function effect of RET mutations causing Hirschsprung disease

B. Pasini, M. G. Borrello, A. Greco, I. Bongarzone, Y. Luo, P. Mondellini, L. Alberti, C. Miranda, E. Arighi, R. Bocciardi, M. Seri, V. Barone, M. T. Radice, G. Romeo, M. A. Pierotti

Research output: Contribution to journalArticlepeer-review


We have introduced three Hirschsprung (HSCR) mutations localized in the tyrosine kinase domain of RET into the RET/PTC2 chimaeric oncogene which is capable of transforming NIH3T3 mouse fibroblasts and of differentiating pC12 rat pheochromocytoma cells. The three HSCR mutations abolished the biological activity of RET/PTC2 in both cell types and significantly decreased its tyrosine phosphorylation. By contrast, a rare polymorphism in exon 18 does not alter the transforming capability of RET/PTC2 or its tyrosine phosphorylation. These data suggest a loss of function effect of HSCR mutations which might act through a dominant negative mechanism. Our model system is therefore capable of discriminating between causative HSCR mutations and rare polymorphisms in the tyrosine kinase domain of RET.

Original languageEnglish
Pages (from-to)35-40
Number of pages6
JournalNature Genetics
Issue number1
Publication statusPublished - 1995

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'Loss of function effect of RET mutations causing Hirschsprung disease'. Together they form a unique fingerprint.

Cite this