Dissection of the MYCN locus in Feingold Syndrome and isolated esophageal atresia

Loic de Pontual (1) , Marie Cognet (1) , Agnès Nougayrede (1) , Valérie Malan (1) , Patrick Callier (1) , David Genevieve (1) , Alice Goldenberg (1) , Delphine Héron (1) , Celia Cretole (1) , Sabine Sarnaki (1) , Laurence Faivre (1) , Sandra Mercier (1) , Sabine Sigaudy (1) , Arnold Munnich (1) , Michel Vekemans (1) , Stanislas Lyonnet (1) , Heather C. Etchevers (1) , Jeanne Amiel (1)

1 Service de génétique [Rouen]

Feingold syndrome (FS) is a syndromic microcephaly entity for which MYCN is the major disease-causing gene. We studied the expression pattern of MYCN at different stages of human embryonic development and collected a series of 17 FS and 12 isolated oesophageal atresia (IOA) cases. A MYCN gene deletion/mutation was identified in 47% of FS cases exclusively. We hypothesized that mutations or deletions of highly conserved non-coding elements (HCNEs) at the MYCN locus could lead to its misregulation and thereby to FS and/or IOA. We subsequently sequenced 5 HCNEs at the MYCN locus and designed a high-density tiling path comparative genomic hybridization array of 3.3 Mb at the MYCN locus. We found no mutations or deletions in this region, supporting the hypothesis of genetic heterogeneity in FS.

Mots clés: Feingold syndrome; MYCN; genetic heterogeneity

Loic de Pontual, Marie Cognet, Agnès Nougayrede, Valérie Malan, Patrick Callier, et al.. Dissection of the MYCN locus in Feingold Syndrome and isolated esophageal atresia. European Journal of Human Genetics, 2011, ⟨10.1038/ejhg.2010.225⟩. ⟨hal-00608020⟩