PMX2B, a new candidate gene for Hirschsprung's disease

Clin Genet. 2003 Sep;64(3):204-9. doi: 10.1034/j.1399-0004.2003.00105.x.


Hirschsprung's (HSCR) disease is a congenital intestinal malformation of the enteric nervous system. It is a multigenic malformation and until now, eight genes have been involved in the etiology of this disease: genes encoding proteins of the RET signaling pathway (RET, GDNF and NTN), genes participating in the endothelin (EDN) type B receptor pathway (EDNRB, EDN3 and ECE-1), the SOX10 gene and the SIP1 gene that is mutated in syndromic forms of HSCR. Mutations of these genes are found in not more than 50-60% of affected individuals. Here, we report on the results of a molecular cytogenetic study performed in a girl who presented with a syndromic short segment HSCR associated with a de novo t(4;8)(p13;p22) translocation. A comparative genomic hybridization (CGH) study found a 4p12p13 deletion. A molecular characterization of this rearrangement showed that the 4p13 deletion was 5 Mb in length and included the paired mesoderm homeobox gene (PMX2B) (MIM 603851), a gene expressed in the human embryonic gut and essential for the development of autonomic neural crest derivatives. The present observation suggests that PMX2B haploinsuffciency might predispose to HSCR.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Aborted Fetus
  • Chromosomes, Human, Pair 4 / genetics
  • Chromosomes, Human, Pair 4 / ultrastructure*
  • Chromosomes, Human, Pair 8 / ultrastructure*
  • Developmental Disabilities / genetics*
  • Enteric Nervous System / embryology
  • Enteric Nervous System / metabolism
  • Face / abnormalities
  • Facial Neoplasms / congenital
  • Facial Neoplasms / genetics
  • Female
  • Gene Deletion*
  • Hemangioma / congenital
  • Hemangioma / genetics
  • Hirschsprung Disease / genetics*
  • Homeodomain Proteins / biosynthesis
  • Homeodomain Proteins / genetics
  • Humans
  • In Situ Hybridization
  • Infant
  • Karyotyping
  • Limb Deformities, Congenital / genetics
  • Nucleic Acid Hybridization
  • RNA, Messenger / biosynthesis
  • Transcription Factors / biosynthesis
  • Transcription Factors / deficiency*
  • Transcription Factors / genetics
  • Translocation, Genetic*


  • Homeodomain Proteins
  • NBPhox protein
  • RNA, Messenger
  • Transcription Factors

Associated data

  • OMIM/603851