MYCN haploinsufficiency is associated with reduced brain size and intestinal atresias in Feingold syndrome.
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.
van Bokhoven
Hans
H
Department of Human Genetics, Radboud University Nijmegen Medical Center, Box 9101, 6500 HB, Nijmegen, The Netherlands. H.vanBokhoven@antrg.umcn.nl <H.vanBokhoven@antrg.umcn.nl>
Celli
Jacopo
J
van Reeuwijk
Jeroen
J
Rinne
Tuula
T
Glaudemans
Bob
B
van Beusekom
Ellen
E
Rieu
Paul
P
Newbury-Ecob
Ruth A
RA
Chiang
Chin
C
Brunner
Han G
HG
D001921:Brain / Q000002:abnormalities*; D004252:DNA Mutational Analysis; D005260:Female; D018628:Gene Dosage; D006579:Heterozygote; D006801:Humans; D007409:Intestinal Atresia / Q000235:genetics*; D008297:Male; D009154:Mutation; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D017422:Sequence Analysis, DNA
C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins