title: Myelomeningocele and Waardenburg syndrome (type 3) in patients with interstitial deletions of 2q35 and the PAX3 gene: possible digenic inheritance of a neural tube defect.
abstract: From a spina bifida clinic we have identified two patients with a syndrome of myelomeningocele and Waardenburg syndrome type 3 (WS3). The patients each possess a single, de novo, interstitial deletion of chromosome 2 (2q35-36.2), including the PAX3 gene. Deletion of PAX3 was confirmed by fluorescence in situ hybridization (FISH). Analysis with PAX3 and flanking microsatellites shows that the deleted interval of chromosome 2 is of paternal origin and is at least 2 and 6 cM in the two patients. Interstitial deletions in this region result in the Waardenburg syndrome (WS1), but have not been associated with neural tube defects (NTDs). Although other etiologies have not been formally excluded, these patients raise the possibility of a digenic etiology of their NTDs via a genetic interaction of the deleted PAX3 gene with a second unidentified locus.
authors.affiliation: Department of Molecular Pharmacology and Biological Chemistry, Northwestern University School of Medicine, Chicago, Illinois 60611, USA. j-nye@nwu.edu
authors.forename: J S
authors.initials: JS
authors.lastname: Nye
authors.forename: N
authors.initials: N
authors.lastname: Balkin
authors.forename: H
authors.initials: H
authors.lastname: Lucas
authors.forename: P A
authors.initials: PA
authors.lastname: Knepper
authors.forename: D G
authors.initials: DG
authors.lastname: McLone
authors.forename: J
authors.initials: J
authors.lastname: Charrow
mesh_terms: D002675:Child, Preschool; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D008591:Meningomyelocele / Q000235:genetics*; D018895:Microsatellite Repeats; D009436:Neural Tube Defects / Q000209:etiology / Q000235:genetics; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D010375:Pedigree; D011110:Polymorphism, Genetic / Q000235:genetics; D014157:Transcription Factors; D014849:Waardenburg Syndrome / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; C068686:Pax3 protein, mouse