Identification of new mutations in the NF2 tumor suppressor gene in schwannomas

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:133509

Guida, M; Welling, B; Prior, T W ^[1]

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1. Ohio State Univ., Columbus, OH (United States)

Neurofibromatosis type 2 (NF2) is a severe genetic disorder with an incidence of approximately 1 in 40,000 individuals and is characterized by the formation of multiple benign nervous system tumors. The clinical hallmark of NF2 is the bilateral occurrence of schwannomas on the eighth cranial nerve (vestibular schwannomas). Recently, it has been shown that loss or inactivation of a tumor suppressor gene located in chromosome band 22q12 is the molecular cause of NF2 tumorigenesis. Also, mutations in the NF2 gene have now been identified in patients with sporadic vestibular schwannomas (unilateral schwannomas). We have completed the screening of 80% of the NF2 coding sequence of DNA from 13 sporadic schwannomas and 2 schwannomas from NF2 patients. Using heteroduplex analysis and direct sequencing, we found 13 novel mutations located in 7 different exons with a small cluster (46% of the mutations) located in the central portion of the gene. All of the mutations were unique to single patients. In three tumors, both NF2 alleles were mutated. The types of mutations found include: small deletions ranging from 1 to 30 base pairs, nonsense mutations, a single missense mutation and a splice donor site alteration. It appears that small deletions are the most common type of NF2 gene mutation. We also have developed a dosage test based on quantitative PCR and hybridization with specific probes to detect the loss of heterozygosity. We found that 7 out of 15 schwannomas (47%) show loss of heterozygosity. We are currently extending the analysis to all of the NF2 exons and DNA from 60 additional schwannomas.

• OSTI ID: 133509
• Report Number(s): CONF-941009--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
CHROMOSOMAL ABERRATIONS
DNA HYBRIDIZATION
DNA SEQUENCING
GENE MUTATIONS
GENES
GENETIC MAPPING
HUMAN CHROMOSOME 22
NEOPLASMS
NERVOUS SYSTEM
NERVOUS SYSTEM DISEASES
PATIENTS
POLYMERASE CHAIN REACTION
PROBES
SPLICING
STATISTICS