Germline deletion in a neurofibromatosis type 2 kindred inactivates the NF2 gene and a candidate meningioma locus

Neurofibromatosis type 2 (NF2) is an autosomal dominant disease which predisposes to the development of schwannomas, meningiomas, ependymomas, and juvenile cataracts. The NF2 gene (NF2) has recently been isolated and maps to chromosome 22q12 between the loci D22S212 and D22S32. Deletion studies in s...

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Bibliographic Details
Published in:Human molecular genetics 1993-08, Vol.2 (8), p.1215-1220
Main Authors: Sanson, Marc, Marineau, Claude, Desmaze, Chantale, Lutchman, Mohini, Ruttledge, Martin, Baron, Chantal, Narod, Steven, Delattre, Olivier, Lenoir, Gilbert, Thomas, Gilles, Aurlas, Alain, Rouleau, Guy A.
Format: Article
Language:English
Subjects:
Biological and medical sciences
Cells, Cultured
chromosome 22
Chromosome Mapping
Chromosomes, Human, Pair 22
Cosmids
deletion
Female
Gene Deletion
Genes, Neurofibromatosis 2
Genetic Markers
Humans
In Situ Hybridization, Fluorescence
inactivation
Lymphocytes - metabolism
Male
man
Medical sciences
Meningeal Neoplasms - genetics
meningioma
Meningioma - genetics
Neurilemmoma - genetics
Neurofibromatosis 2 - genetics
Neurofilament Proteins - genetics
Neurology
NF2 gene
Oligonucleotide Probes
Pedigree
Recklinghausen's disease
Restriction Mapping
tumor suppressor genes
Tumors of the nervous system. Phacomatoses
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Summary:Neurofibromatosis type 2 (NF2) is an autosomal dominant disease which predisposes to the development of schwannomas, meningiomas, ependymomas, and juvenile cataracts. The NF2 gene (NF2) has recently been isolated and maps to chromosome 22q12 between the loci D22S212 and D22S32. Deletion studies in sporadic and NF2 associated schwannomas and meningiomas, and the presence of Inactivating mutations in NF2 in patients suggest that it acts as a tumor suppressor gene. A candidate meningioma gene (MEN) has also been isolated from the same Interval. A new highly polymorphic (CA)n marker, D22S268, which maps very near to NF2, has allowed us to Identify a kindred with three living affected individuals, where the disease Is presumably caused by a large germline deletion. Fluorescence in situ hybridization and pulsed field gel electrophoresis confirm the presence of a 700kb deletion which includes the neurofllament heavy chain subunit gene locus (NEFH), D22S268, NF2 and the putative MEN gene. The absence of meningiomas In this pedigree raises doubts as to the existence of a separate MEN locus In this region. These results support the hypothesis that NF2 results from the Inactivation of a tumor suppressor gene on chromosome 22q.
ISSN:0964-6906
1460-2083
DOI:10.1093/hmg/2.8.1215