title: A duplication/paracentric inversion associated with familial X-linked deafness (DFN3) suggests the presence of a regulatory element more than 400 kb upstream of the POU3F4 gene.
abstract: X-linked deafness with stapes fixation (DFN3) is caused by mutations in the POU3F4 gene at Xq21.1. By employing pulsed field gel electrophoresis (PFGE) we identified a chromosomal aberration in the DNA of a DFN3 patient who did not show alterations in the open reading frame (ORF) of POU3F4. Southern blot analysis indicated that a DNA segment of 150 kb, located 170 kb proximal to the POU3F4 gene, was duplicated. Fluorescence in situ hybridization (FISH) analysis, PFGE, and detailed Southern analysis revealed that this duplication is part of a more complex rearrangement including a paracentric inversion involving the Xq21.1 region, and presumably the Xq21.3 region. Since at least two DFN3-associated minideletions are situated proximal to the duplicated segment, the inversion most likely disconnects the POU3F4 gene from a regulatory element which is located at a distance of at least 400 kb upstream of the POU3F4 gene.
authors.affiliation: Department of Human Genetics, University Hospital Nijmegen, The Netherlands.
authors.forename: Y J
authors.initials: YJ
authors.lastname: de Kok
authors.forename: G F
authors.initials: GF
authors.lastname: Merkx
authors.forename: S M
authors.initials: SM
authors.lastname: van der Maarel
authors.forename: I
authors.initials: I
authors.lastname: Huber
authors.forename: S
authors.initials: S
authors.lastname: Malcolm
authors.forename: H H
authors.initials: HH
authors.lastname: Ropers
authors.forename: F P
authors.initials: FP
authors.lastname: Cremers
mesh_terms: D015139:Blotting, Southern; D007446:Chromosome Inversion; D002874:Chromosome Mapping; D003638:Deafness / Q000235:genetics*; D016521:Electrophoresis, Gel, Pulsed-Field; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D005810:Multigene Family; D050809:POU Domain Factors; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics*; D015854:Up-Regulation; D014960:X Chromosome
chemical_list: D050809:POU Domain Factors; C091774:POU3F4 protein, human; D014157:Transcription Factors