title: PMX2B, a new candidate gene for Hirschsprung's disease.
abstract: 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.
authors.affiliation: Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: H K
authors.initials: HK
authors.lastname: Benailly
authors.forename: J M
authors.initials: JM
authors.lastname: Lapierre
authors.forename: B
authors.initials: B
authors.lastname: Laudier
authors.forename: J
authors.initials: J
authors.lastname: Amiel
authors.forename: T
authors.initials: T
authors.lastname: Attié
authors.forename: M C
authors.initials: MC
authors.lastname: De Blois
authors.forename: M
authors.initials: M
authors.lastname: Vekemans
authors.forename: S P
authors.initials: SP
authors.lastname: Romana
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D037881:Aborted Fetus; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics / Q000648:ultrastructure*; D002898:Chromosomes, Human, Pair 8 / Q000648:ultrastructure*; D002658:Developmental Disabilities / Q000235:genetics*; D017615:Enteric Nervous System / Q000196:embryology / Q000378:metabolism; D005145:Face / Q000002:abnormalities; D005153:Facial Neoplasms / Q000151:congenital / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D006391:Hemangioma / Q000151:congenital / Q000235:genetics; D006627:Hirschsprung Disease / Q000235:genetics*; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D007223:Infant; D007621:Karyotyping; D017880:Limb Deformities, Congenital / Q000235:genetics; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: D018398:Homeodomain Proteins; C109220:NBPhox protein; D012333:RNA, Messenger; D014157:Transcription Factors