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.
Subscribe to Journal
Get full journal access for 1 year
only $18.75 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Torfs, C.P. et al. Teratology 52, 220–232 (1995).
Merei, J.M. & Hutson, J.M. Pediatr. Surg. Int. 18, 319–326 (2002).
Celli, J. et al. Am. J. Hum. Genet. 66, 436–444 (2000).
Celli, J. et al. Am. J. Med. Genet. 122A, 294–300 (2003).
Dib, C. et al. Nature 380, 152–154 (1996).
Litingtung, Y. et al. Nat. Genet. 20, 58–61 (1998).
Kenney, A.M. et al. Development 130, 15–28 (2003).
Oliver, T.G. et al. Proc. Natl. Acad. Sci. USA 100, 7331–7336 (2003).
Dang, C.V. et al. Proc. Natl. Acad. Sci. USA 89, 599–602 (1992).
Nair, S.K. et al. Cell 112, 193–205 (2003).
Jopling, C.L. & Willis, A.E. Oncogene 20, 2664–2670 (2001).
Hirvonen, H. et al. Oncogene 5, 1787–1797 (1990).
Stanton, B.R. et al. Genes Dev. 6, 2235–2247 (1992).
Moens, C.B. et al. Genes Dev. 6, 691–704 (1992).
Knoepfler, P.S. et al. Genes Dev. 16, 2699–2712 (2002).
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.
The authors declare no competing financial interests.
Heterozygous MYCN mutations in Feingold syndrome patients. (PDF 29 kb)
Predicted protein structure of the B-HLH/Leu-Z domain of MYCN. (PDF 215 kb)
Segregation of the R373X mutation in a large FS family. (PDF 23 kb)
MLPA-based microdeletion analysis of the MYCN gene. (PDF 18 kb)
MYCN immunoblot analysis of human fetal tissues. (PDF 33 kb)
About this article
Cite this article
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
Identification of rare heterozygous missense mutations in FANCA in esophageal atresia patients using next-generation sequencing
Neuroscience Bulletin (2018)
American Journal of Medical Genetics Part A (2018)
Genetic variants of MGMT, RHPN2, and FAM49A contributed to susceptibility of nonsyndromic orofacial clefts in a Chinese population
Journal of Oral Pathology & Medicine (2018)
Developmental Biology (2017)