title: High resolution deletion analysis of constitutional DNA from neurofibromatosis type 2 (NF2) patients using microarray-CGH.
abstract: 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.
authors.affiliation: Department of Molecular Medicine, CMM Building L8, Karolinska Hospital, SE-17176 Stockholm, Sweden.
authors.forename: C E
authors.initials: CE
authors.lastname: Bruder
authors.forename: C
authors.initials: C
authors.lastname: Hirvelä
authors.forename: I
authors.initials: I
authors.lastname: Tapia-Paez
authors.forename: I
authors.initials: I
authors.lastname: Fransson
authors.forename: R
authors.initials: R
authors.lastname: Segraves
authors.forename: G
authors.initials: G
authors.lastname: Hamilton
authors.forename: X X
authors.initials: XX
authors.lastname: Zhang
authors.forename: D G
authors.initials: DG
authors.lastname: Evans
authors.forename: A J
authors.initials: AJ
authors.lastname: Wallace
authors.forename: M E
authors.initials: ME
authors.lastname: Baser
authors.forename: J
authors.initials: J
authors.lastname: Zucman-Rossi
authors.forename: M
authors.initials: M
authors.lastname: Hergersberg
authors.forename: E
authors.initials: E
authors.lastname: Boltshauser
authors.forename: L
authors.initials: L
authors.lastname: Papi
authors.forename: G A
authors.initials: GA
authors.lastname: Rouleau
authors.forename: G
authors.initials: G
authors.lastname: Poptodorov
authors.forename: A
authors.initials: A
authors.lastname: Jordanova
authors.forename: H
authors.initials: H
authors.lastname: Rask-Andersen
authors.forename: L
authors.initials: L
authors.lastname: Kluwe
authors.forename: V
authors.initials: V
authors.lastname: Mautner
authors.forename: M
authors.initials: M
authors.lastname: Sainio
authors.forename: G
authors.initials: G
authors.lastname: Hung
authors.forename: T
authors.initials: T
authors.lastname: Mathiesen
authors.forename: C
authors.initials: C
authors.lastname: Möller
authors.forename: S M
authors.initials: SM
authors.lastname: Pulst
authors.forename: H
authors.initials: H
authors.lastname: Harder
authors.forename: A
authors.initials: A
authors.lastname: Heiberg
authors.forename: M
authors.initials: M
authors.lastname: Honda
authors.forename: M
authors.initials: M
authors.lastname: Niimura
authors.forename: S
authors.initials: S
authors.lastname: Sahlén
authors.forename: E
authors.initials: E
authors.lastname: Blennow
authors.forename: D G
authors.initials: DG
authors.lastname: Albertson
authors.forename: D
authors.initials: D
authors.lastname: Pinkel
authors.forename: J P
authors.initials: JP
authors.lastname: Dumanski
mesh_terms: D000293:Adolescent; D002648:Child; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D003001:Cloning, Molecular; D020451:Contig Mapping; D004247:DNA / Q000737:chemistry / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D016518:Neurofibromatosis 2 / Q000235:genetics* / Q000473:pathology; D025581:Neurofibromin 2; D009693:Nucleic Acid Hybridization / Q000379:methods; D017422:Sequence Analysis, DNA
chemical_list: D008565:Membrane Proteins; D025581:Neurofibromin 2; D004247:DNA