Germline mutations of the paired-like homeobox 2B (PHOX2B) gene in neuroblastoma

Am J Hum Genet. 2004 Apr;74(4):761-4. doi: 10.1086/383253. Epub 2004 Mar 11.


Neuroblastoma (NB) is a frequent pediatric tumor for which recurrent somatic rearrangements are known. Germline mutations of predisposing gene(s) are suspected on the basis of rare familial cases and the association of NB with other genetically determined congenital malformations of neural crest-derived cells--namely, Hirschsprung disease (HSCR) and/or congenital central hypoventilation syndrome (CCHS). We recently identified the paired-like homeobox 2B (PHOX2B) gene as the major disease-causing gene in isolated and syndromic CCHS, which prompted us to regard it as a candidate gene in NB. Here, we report on germline mutations of PHOX2B in both a familial case of NB and a patient with the HSCR-NB association. PHOX2B, therefore, stands as the first gene for which germline mutations predispose to NB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Germ-Line Mutation / genetics*
  • Homeodomain Proteins / genetics*
  • Humans
  • Male
  • Neuroblastoma / genetics*
  • Pedigree
  • Transcription Factors / genetics*


  • Homeodomain Proteins
  • NBPhox protein
  • Transcription Factors

Associated data

  • OMIM/142623
  • OMIM/209880
  • OMIM/256700
  • OMIM/603851