caa a22 4500 397575890 CHVBK 20180308164856.0 cr unu---uuuuu 161202e199609 xx s 000 0 eng 10.1093/hmg/5.9.1229 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.9.1229 Identification of a Hot Spot for Microdeletions in Patients with X-linked Deafness Type 3 (DFN3) 900 kb Proximal to the DFN3 gene POU3F4 [Elektronische Daten] [Yvette J. M. de Kok, Erik R. Vossenaar, Cor W. R. J. Cremers, Niklas Dahl, Jocelyn Laporte, Ling Jia Hu, Didier Lacombe, Nathan Fischel-Ghodsian, Rick A. Friedman, Lorne S. Parnes, Peter Thorpe, Maria Bitner-Glindzicz, Hans-Jürgen Pander, Helmut Heilbronner, Johanna Graveline, Johan T. den Dunnen, Han G. Brunner, Hans-Hilger Ropers, Frans P. M. Cremers] Small mutations in the POU domain gene POU3F4 were recently shown to cause X-linked deafness type 3 (DFN3) in nine unrelated males. The POU3F4 gene was found to be located outside four of five deletions associated with DFN3. Two of these deletions were situated more than 400 kb proximal to POU3F4. Employing PCR analysis of sequence tagged sites from this region we initially identified novel deletions in two DFN3 patients. To investigate this chromosomal segment in more detail, we extended a previously established 850 kb cosmid contig in the centromeric direction to a total size of 1500 kb. Cosmids from this contig were hybridized to DNA of 11 unrelated males with DFN3. In two patients, we identified deletions encompassing the POU3F4 gene and variably sized segments of Xq21.1. In six of the nine remaining patients which lacked mutations in the POU3F4 gene, smaller deletions were identified which, with one exception, overlap in a 8 kb segment 900 kb proximal to the POU3F4 gene. In one patient, we identified several small deletions in the vicinity of the 8 kb DNA segment. Together, deletions account for 56% (13/23) of all known DFN3 mutations, most (10/13) of which do not encompass the POU3F4 gene. The combined molecular data suggest that the deletion hot spot region in Xq21.1 contains another DFN3 gene or, alternatively, a sequence element involved in transcriptional regulation of POU3F4. © 1996 Oxford University Press de Kok Yvette J. M. Department of Human Genetics, University Hospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands aut Vossenaar Erik R. Department of Human Genetics, University Hospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands aut Cremers Cor W. R. J. Department of Otorhinolaryngology, University Hospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands aut Dahl Niklas Department of Clinical Genetics, Uppsala University Children's Hospital, S-751 85 Uppsala, Sweden aut Laporte Jocelyn Department of Human Genetics, Institut de Génétique et de Biologie Moleculaire et Cellulaire, Université Louis Pasteur, Parc d'Innovation 1, rue Laurent Fries, Illkirch, C.U. de Strasbourg, France aut Jia Hu Ling Department of Human Genetics, Institut de Génétique et de Biologie Moleculaire et Cellulaire, Université Louis Pasteur, Parc d'Innovation 1, rue Laurent Fries, Illkirch, C.U. de Strasbourg, France aut Lacombe Didier Groupe Hospitalier Pellegrin, CHRU Bordeaux, Place Amélie Raba-Léon, 33076, Bordeaux Cédex, France aut Fischel-Ghodsian Nathan Department of Pediatrics, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048-0750, USA aut Friedman Rick A. Department of Otolaryngology, University of Cincinnati, 670528, Cincinnati, OH 45267, USA aut Parnes Lorne S. Department of Otolaryngology, University Hospital, 339 Windermere Road, London, Ontario N6A 5A5, Canada aut Thorpe Peter Department of Diagnostic Imaging, James Paton Memorial Hospital, 125 Trans Canada Highway, Gander A1V 1P7, Newfoundland, Canada aut Bitner-Glindzicz Maria Institute of Child Health, University of London, 30 Guilford Street, London WC1N 1EH, UK aut Pander Hans-Jürgen Frauenklinik Berg, Department of Clinical Genetics, D-70190 Stuttgart, Germany aut Heilbronner Helmut Frauenklinik Berg, Department of Clinical Genetics, D-70190 Stuttgart, Germany aut Graveline Johanna Department of Human Genetics, The Mount Sinai Medical Center, One Gustave L. Levy Place, New York, NY 10029-6574, USA aut den Dunnen Johan T. Department of Human Genetics, Silvius Laboratorium, P.O.Box 9503, Leiden, The Netherlands aut Brunner Han G. Department of Human Genetics, University Hospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands aut Ropers Hans-Hilger Department of Human Genetics, University Hospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands aut Cremers Frans P. M. Department of Human Genetics, University Hospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands aut Human Molecular Genetics Oxford University Press 5/9(1996-09), 1229-1235 0964-6906 5:9<1229 1996 5 hmg https://doi.org/10.1093/hmg/5.9.1229 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.9.1229 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- de Kok Yvette J. M. Department of Human Genetics, University Hospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands aut NATIONALLICENCE 700 1- Vossenaar Erik R. Department of Human Genetics, University Hospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands aut NATIONALLICENCE 700 1- Cremers Cor W. R. J. Department of Otorhinolaryngology, University Hospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands aut NATIONALLICENCE 700 1- Dahl Niklas Department of Clinical Genetics, Uppsala University Children's Hospital, S-751 85 Uppsala, Sweden aut NATIONALLICENCE 700 1- Laporte Jocelyn Department of Human Genetics, Institut de Génétique et de Biologie Moleculaire et Cellulaire, Université Louis Pasteur, Parc d'Innovation 1, rue Laurent Fries, Illkirch, C.U. de Strasbourg, France aut NATIONALLICENCE 700 1- Jia Hu Ling Department of Human Genetics, Institut de Génétique et de Biologie Moleculaire et Cellulaire, Université Louis Pasteur, Parc d'Innovation 1, rue Laurent Fries, Illkirch, C.U. de Strasbourg, France aut NATIONALLICENCE 700 1- Lacombe Didier Groupe Hospitalier Pellegrin, CHRU Bordeaux, Place Amélie Raba-Léon, 33076, Bordeaux Cédex, France aut NATIONALLICENCE 700 1- Fischel-Ghodsian Nathan Department of Pediatrics, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048-0750, USA aut NATIONALLICENCE 700 1- Friedman Rick A. Department of Otolaryngology, University of Cincinnati, 670528, Cincinnati, OH 45267, USA aut NATIONALLICENCE 700 1- Parnes Lorne S. Department of Otolaryngology, University Hospital, 339 Windermere Road, London, Ontario N6A 5A5, Canada aut NATIONALLICENCE 700 1- Thorpe Peter Department of Diagnostic Imaging, James Paton Memorial Hospital, 125 Trans Canada Highway, Gander A1V 1P7, Newfoundland, Canada aut NATIONALLICENCE 700 1- Bitner-Glindzicz Maria Institute of Child Health, University of London, 30 Guilford Street, London WC1N 1EH, UK aut NATIONALLICENCE 700 1- Pander Hans-Jürgen Frauenklinik Berg, Department of Clinical Genetics, D-70190 Stuttgart, Germany aut NATIONALLICENCE 700 1- Heilbronner Helmut Frauenklinik Berg, Department of Clinical Genetics, D-70190 Stuttgart, Germany aut NATIONALLICENCE 700 1- Graveline Johanna Department of Human Genetics, The Mount Sinai Medical Center, One Gustave L. Levy Place, New York, NY 10029-6574, USA aut NATIONALLICENCE 700 1- den Dunnen Johan T. Department of Human Genetics, Silvius Laboratorium, P.O.Box 9503, Leiden, The Netherlands aut NATIONALLICENCE 700 1- Brunner Han G. Department of Human Genetics, University Hospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands aut NATIONALLICENCE 700 1- Ropers Hans-Hilger Department of Human Genetics, University Hospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands aut NATIONALLICENCE 700 1- Cremers Frans P. M. Department of Human Genetics, University Hospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/9(1996-09), 1229-1235 0964-6906 5:9<1229 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford