Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (98)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Bruder, C. E.G.
Right arrow Articles by Dumanski, J. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bruder, C. E.G.
Right arrow Articles by Dumanski, J. P.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, 2001, Vol. 10, No. 3 271-282
© 2001 Oxford University Press

High resolution deletion analysis of constitutional DNA from neurofibromatosis type 2 (NF2) patients using microarray-CGH

Carl E.G. Bruder1, Carina Hirvelä2, Isabel Tapia-Paez1, Ingegerd Fransson1, Richard Segraves3, Greg Hamilton3, Xiao Xiao Zhang3, D. Gareth Evans4, Andrew J. Wallace4, Michael E. Baser5, Jessica Zucman-Rossi6, Martin Hergersberg7, Eugene Boltshauser8, Laura Papi9, Guy A. Rouleau10, George Poptodorov11, Albena Jordanova12, Helge Rask-Andersen2, Lan Kluwe13, Victor Mautner13, Markku Sainio14, Gene Hung15, Tiit Mathiesen16, Claes Möller17, Stefan M. Pulst18, Henrik Harder19, Arvid Heiberg20, Mariko Honda21, Michihito Niimura21, Sigrid Sahlén1, Elisabeth Blennow1, Donna G. Albertson22, Daniel Pinkel3 and Jan P. Dumanski1,23,+

1Department of Molecular Medicine, CMM Building L8, Karolinska Hospital, SE-17176 Stockholm, Sweden, 2Department of Otorhinolaryngology and Head and Neck Surgery, Uppsala University Hospital, SE-75185 Uppsala, Sweden, 3Department of Laboratory Medicine, UCSF Cancer Center, Box 0808, UCSF, San Francisco, CA 94143-0808, USA, 4Department of Medical Genetics, St Mary’s Hospital, Hathersage Road, Manchester M13 0JH, UK, 511746 Bellagio Road, 308, Los Angeles, CA 90049, USA, 6Laboratorie de Geneticque des Tumeurs, INSERM U434, 27 rue Juliette Dodu, F-75010 Paris, France, 7Institute of Medical Genetics, University of Zürich, Rämistrasse 74, CH-8001 Zürich, Switzerland, 8Division of Pediatric Neurology, Children Hospital, Steinweisstrasse 75, CH-8032 Zürich, Switzerland, 9Medical Genetics Unit, Department of Physiopathology, University of Florence, Viale Pieraccini 6, I-500139 Florence, Italy, 10Centre for Research in Neuroscience, Montreal General Hospital, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4, Canada, 11Department of Neurosurgery, University Hospital Queen Giovanna, 8 Belo More Street, BG-1527 Sofia, Bulgaria, 12Laboratory of Molecular Pathology, 2 Zdrave Strasse, BG-1431, Sofia, Bulgaria, 13Department of Neurology, Klinikum Nord Ochsenzoll, Langenhorner Ch560, D-22419 Hamburg, Germany, 14Department of Pathology, University of Helsinki, Haartman Institute, FIN-00014 Helsinki, Finland, 15House Ear Institute, 2100 West Third Street, Los Angeles, CA 90057, USA, 16Department of Neurosurgery, Karolinska Hospital, Box 130, SE-17176 Stockholm, Sweden, 17Department of Audiology, Sahlgrenska University Hospital, SE-41335 Göteborg, Sweden, 18Division of Neurology, Cedars-Sinai Medical Center, 8631 West 3rd Street 1145E, Los Angeles, CA 90048, USA, 19Department of Otorhinolaryngology, Linköping University Hospital, SE-58185 Linköping, Sweden, 20Department of Medical Genetics, Piestredet 32, Rikshospitalet, 0027 Oslo, Norway, 21Department of Dermatology, The Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan, 22Cancer Research Institute, UCSF Cancer Center, Box 0808, UCSF, San Francisco, CA 94143-0808, USA and 23Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University Hospital, SE-75185 Uppsala, Sweden

Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder whose hallmark is bilateral vestibular schwannoma. It displays a pronounced clinical heterogeneity with mild to severe forms. The NF2 tumor suppressor (merlin/schwannomin) has been cloned and extensively analyzed for mutations in patients with different clinical variants of the disease. Correlation between the type of the NF2 gene mutation and the patient phenotype has been suggested to exist. However, several independent studies have shown that a fraction of NF2 patients with various phenotypes have constitutional deletions that partly or entirely remove one copy of the NF2 gene. The purpose of this study was to examine a 7 Mb interval in the vicinity of the NF2 gene in a large series of NF2 patients in order to determine the frequency and extent of deletions. A total of 116 NF2 patients were analyzed using high-resolution array-comparative genomic hybridization (CGH) on an array covering at least 90% of this region of 22q around the NF2 locus. Deletions, which remove one copy of the entire gene or are predicted to truncate the schwannomin protein, were detected in 8 severe, 10 moderate and 6 mild patients. This result does not support the correlation between the type of mutation affecting the NF2 gene and the disease phenotype. This work also demonstrates the general usefulness of the array-CGH methodology for rapid and comprehensive detection of small (down to 40 kb) heterozygous and/or homozygous deletions occurring in constitutional or tumor-derived DNA.

+ To whom correspondence should be addressed at: Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University Hospital, SE-75185 Uppsala, Sweden. Tel: +46 18 4714814; Fax: +46 18 558931; Email: jan.dumanski@genpat.uu.se


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Eur Heart JHome page
B. Thienpont, L. Mertens, T. de Ravel, B. Eyskens, D. Boshoff, N. Maas, J.-P. Fryns, M. Gewillig, J. R. Vermeesch, and K. Devriendt
Submicroscopic chromosomal imbalances detected by array-CGH are a frequent cause of congenital heart defects in selected patients
Eur. Heart J., November 2, 2007; 28(22): 2778 - 2784.
[Abstract] [Full Text] [PDF]

Home page
 J. Mol. Diagn.Home page
B. A. Bejjani and L. G. Shaffer
Application of Array-Based Comparative Genomic Hybridization to Clinical Diagnostics
J. Mol. Diagn., November 1, 2006; 8(5): 528 - 533.
[Abstract] [Full Text] [PDF]

Home page
 J. Mol. Diagn.Home page
G. Mohapatra, R. A. Betensky, E. R. Miller, B. Carey, L. D. Gaumont, D. A. Engler, and D. N. Louis
Glioma Test Array for Use with Formalin-Fixed, Paraffin-Embedded Tissue: Array Comparative Genomic Hybridization Correlates with Loss of Heterozygosity and Fluorescence in Situ Hybridization
J. Mol. Diagn., May 1, 2006; 8(2): 268 - 276.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
A Slavotinek, S S Lee, R Davis, A Shrit, K A Leppig, J Rhim, K Jasnosz, D Albertson, and D Pinkel
Fryns syndrome phenotype caused by chromosome microdeletions at 15q26.2 and 8p23.1
J. Med. Genet., September 1, 2005; 42(9): 730 - 736.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
M E Baser, L Kuramoto, R Woods, H Joe, J M Friedman, A J Wallace, R T Ramsden, S Olschwang, E Bijlsma, M Kalamarides, et al.
The location of constitutional neurofibromatosis 2 (NF2) splice site mutations is associated with the severity of NF2
J. Med. Genet., July 1, 2005; 42(7): 540 - 546.
[Abstract] [Full Text] [PDF]

Home page
 J. Histochem. Cytochem.Home page
J. R. Vermeesch, C. Melotte, G. Froyen, S. Van Vooren, B. Dutta, N. Maas, S. Vermeulen, B. Menten, F. Speleman, B. De Moor, et al.
Molecular Karyotyping: Array CGH Quality Criteria for Constitutional Genetic Diagnosis
J. Histochem. Cytochem., March 1, 2005; 53(3): 413 - 422.
[Abstract] [Full Text] [PDF]

Home page
 J. Mol. Diagn.Home page
R. Diebold, B. Bartelt-Kirbach, D. G. Evans, D. Kaufmann, and C. O. Hanemann
Sensitive Detection of Deletions of One or More Exons in the Neurofibromatosis Type 2 (NF2) Gene by Multiplexed Gene Dosage Polymerase Chain Reaction
J. Mol. Diagn., February 1, 2005; 7(1): 97 - 104.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
C Le Caignec, M Boceno, P Saugier-Veber, S Jacquemont, M Joubert, A David, T Frebourg, and J M Rival
Detection of genomic imbalances by array based comparative genomic hybridisation in fetuses with multiple malformations
J. Med. Genet., February 1, 2005; 42(2): 121 - 128.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
J. Cardoso, L. Molenaar, R. X. de Menezes, C. Rosenberg, H. Morreau, G. Moslein, R. Fodde, and J. M. Boer
Genomic profiling by DNA amplification of laser capture microdissected tissues and array CGH
Nucleic Acids Res., October 28, 2004; 32(19): e146 - e146.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
N M Solomon, S A Ross, T Morgan, J L Belsky, F A Hol, P S Karnes, N J Hopwood, S E Myers, A S Tan, G L Warne, et al.
Array comparative genomic hybridisation analysis of boys with X linked hypopituitarism identifies a 3.9 Mb duplicated critical region at Xq27 containing SOX3
J. Med. Genet., September 1, 2004; 41(9): 669 - 678.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
M. Guillaud-Bataille, A. Valent, P. Soularue, C. Perot, M.-d.-M. Inda, A. Receveur, S. Smaili, H. R. Crollius, J. Benard, A. Bernheim, et al.
Detecting single DNA copy number variations in complex genomes using one nanogram of starting DNA and BAC-array CGH
Nucleic Acids Res., July 29, 2004; 32(13): e112 - e112.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
P. L. Paris, A. Andaya, J. Fridlyand, A. N. Jain, V. Weinberg, D. Kowbel, J. H. Brebner, J. Simko, J.E. V. Watson, S. Volik, et al.
Whole genome scanning identifies genotypes associated with recurrence and metastasis in prostate tumors
Hum. Mol. Genet., July 1, 2004; 13(13): 1303 - 1313.
[Abstract] [Full Text] [PDF]

Home page
 Hum Reprod UpdateHome page
L. G. Shaffer and B. A. Bejjani
A cytogeneticist's perspective on genomic microarrays
Hum. Reprod. Update, May 1, 2004; 10(3): 221 - 226.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. Heidenblad, E. F. P. M. Schoenmakers, T. Jonson, L. Gorunova, J. A. Veltman, A. G. van Kessel, and M. Hoglund
Genome-Wide Array-Based Comparative Genomic Hybridization Reveals Multiple Amplification Targets and Novel Homozygous Deletions in Pancreatic Carcinoma Cell Lines
Cancer Res., May 1, 2004; 64(9): 3052 - 3059.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
C Shaw-Smith, R Redon, L Rickman, M Rio, L Willatt, H Fiegler, H Firth, D Sanlaville, R Winter, L Colleaux, et al.
Microarray based comparative genomic hybridisation (array-CGH) detects submicroscopic chromosomal deletions and duplications in patients with learning disability/mental retardation and dysmorphic features
J. Med. Genet., April 1, 2004; 41(4): 241 - 248.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
C. J. Shaw and J. R. Lupski
Implications of human genome architecture for rearrangement-based disorders: the genomic basis of disease
Hum. Mol. Genet., April 1, 2004; 13(90001): R57 - 64.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
C J Shaw, C A Shaw, W Yu, P Stankiewicz, L D White, A L Beaudet, and J R Lupski
Comparative genomic hybridisation using a proximal 17p BAC/PAC array detects rearrangements responsible for four genomic disorders
J. Med. Genet., February 1, 2004; 41(2): 113 - 119.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
N Harada, E Hatchwell, N Okamoto, M Tsukahara, K Kurosawa, H Kawame, T Kondoh, H Ohashi, R Tsukino, Y Kondoh, et al.
Subtelomere specific microarray based comparative genomic hybridisation: a rapid detection system for cryptic rearrangements in idiopathic mental retardation
J. Med. Genet., February 1, 2004; 41(2): 130 - 136.
[Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
C. Schwaenen, M. Nessling, S. Wessendorf, T. Salvi, G. Wrobel, B. Radlwimmer, H. A. Kestler, C. Haslinger, S. Stilgenbauer, H. Dohner, et al.
Automated array-based genomic profiling in chronic lymphocytic leukemia: Development of a clinical tool and discovery of recurrent genomic alterations
PNAS, January 27, 2004; 101(4): 1039 - 1044.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
M E Baser, L Kuramoto, H Joe, J M Friedman, A J Wallace, R T Ramsden, and D G R Evans
Genotype-phenotype correlations for cataracts in neurofibromatosis 2
J. Med. Genet., October 1, 2003; 40(10): 758 - 760.
[Full Text] [PDF]

Home page
 J. Med. Genet.Home page
A Moyhuddin, M E Baser, C Watson, S Purcell, R T Ramsden, A Heiberg, A J Wallace, and D G R Evans
Somatic mosaicism in neurofibromatosis 2: prevalence and risk of disease transmission to offspring
J. Med. Genet., June 1, 2003; 40(6): 459 - 463.
[Full Text] [PDF]

Home page
 Genome ResHome page
D. P. Locke, R. Segraves, L. Carbone, N. Archidiacono, D. G. Albertson, D. Pinkel, and E. E. Eichler
Large-Scale Variation Among Human and Great Ape Genomes Determined by Array Comparative Genomic Hybridization
Genome Res., March 1, 2003; 13(3): 347 - 357.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
P. L. Paris, D. G. Albertson, J. C. Alers, A. Andaya, P. Carroll, J. Fridlyand, A. N. Jain, S. Kamkar, D. Kowbel, P.-J. Krijtenburg, et al.
High-Resolution Analysis of Paraffin-Embedded and Formalin-Fixed Prostate Tumors Using Comparative Genomic Hybridization to Genomic Microarrays
Am. J. Pathol., March 1, 2003; 162(3): 763 - 770.
[Abstract] [Full Text] [PDF]

Home page
 Genome ResHome page
J. M. Lage, J. H. Leamon, T. Pejovic, S. Hamann, M. Lacey, D. Dillon, R. Segraves, B. Vossbrinck, A. Gonzalez, D. Pinkel, et al.
Whole Genome Analysis of Genetic Alterations in Small DNA Samples Using Hyperbranched Strand Displacement Amplification and Array-CGH
Genome Res., February 1, 2003; 13(2): 294 - 307.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
P. G. Buckley, K. K. Mantripragada, M. Benetkiewicz, I. Tapia-Paez, T. Diaz de Stahl, M. Rosenquist, H. Ali, C. Jarbo, C. de Bustos, C. Hirvela, et al.
A full-coverage, high-resolution human chromosome 22 genomic microarray for clinical and research applications
Hum. Mol. Genet., December 1, 2002; 11(25): 3221 - 3229.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Chem.Home page
R. Peoples, H. Weltman, R. Van Atta, J. Wang, M. Wood, M. Ferrante-Raimondi, P. Cheng, and B. Huan
High-Throughput Detection of Submicroscopic Deletions and Methylation Status at 15q11-q13 by a Photo-Cross-Linking Oligonucleotide Hybridization Assay
Clin. Chem., October 1, 2002; 48(10): 1844 - 1850.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
S. Mohr, G. D. Leikauf, G. Keith, and B. H. Rihn
Microarrays as Cancer Keys: An Array of Possibilities
J. Clin. Oncol., July 15, 2002; 20(14): 3165 - 3175.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
A.-M. Bashour, J.-J. Meng, W. Ip, M. MacCollin, and N. Ratner
The Neurofibromatosis Type 2 Gene Product, merlin, Reverses the F-Actin Cytoskeletal Defects in Primary Human Schwannoma Cells
Mol. Cell. Biol., February 15, 2002; 22(4): 1150 - 1157.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
G Barbi, E Rossier, S Vossbeck, H Hummler, D Lang, F Flock, R Terinde, J Wirth, W Vogel, and H Kehrer-Sawatzki
Constitutional de novo interstitial deletion of 8 Mb on chromosome 22q12.1-12.3 encompassing the neurofibromatosis type 2 (NF2) locus in a dysmorphic girl with severe malformations
J. Med. Genet., February 1, 2002; 39(2): e6 - 6.
[Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.