MYCN haploinsufficiency is associated with reduced brain size and intestinal atresias in Feingold syndrome

Abstract

Feingold syndrome is characterized by variable combinations of esophageal and duodenal atresias, microcephaly, learning disability, syndactyly and cardiac defect. We show here that heterozygous mutations in the gene MYCN are present in Feingold syndrome. All mutations are predicted to disrupt both the full-length protein and a new shortened MYCN isoform, suggesting that multiple aspects of early embryogenesis and postnatal brain growth in humans are tightly regulated by MYCN dosage.

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Figure 1: Mapping of a new microdeletion in a family with Feingold syndrome.
Figure 2: Localization of mutations in MYCN and the corresponding protein.

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Acknowledgements

We thank the families for contributing material for this study; R. Carozzo, W. Courtens, M. Frydman, P. van Galen, R. Hennekam, H. Kingston, R. Koenig, A. Norman, L. Piersall, T. Prescott and R. Winter for making materials available to us; J. Schouten for the oncogene MLPA kit; and G. Vriend for making the MYCN structural model. This work was supported by grants from the ZON-MW and the Maag Lever Darm Stichting.

Author information

Correspondence to Hans van Bokhoven.

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Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Heterozygous MYCN mutations in Feingold syndrome patients. (PDF 29 kb)

Supplementary Fig. 2

Predicted protein structure of the B-HLH/Leu-Z domain of MYCN. (PDF 215 kb)

Supplementary Fig. 3

Segregation of the R373X mutation in a large FS family. (PDF 23 kb)

Supplementary Fig. 4

MLPA-based microdeletion analysis of the MYCN gene. (PDF 18 kb)

Supplementary Fig. 5

MYCN immunoblot analysis of human fetal tissues. (PDF 33 kb)

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van Bokhoven, H., Celli, J., van Reeuwijk, J. et al. MYCN haploinsufficiency is associated with reduced brain size and intestinal atresias in Feingold syndrome. Nat Genet 37, 465–467 (2005) doi:10.1038/ng1546

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