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. 1994 Aug;55(2):314–320.

Mutational Analysis of Patients with Neurofibromatosis 2

Mia MacCollin, Vijaya Ramesh, Lee B Jacoby, David N Louis, Mari-Paz Rubio, Karen Pulaski, James A Trofatter, M Priscilla Short, Catherine Bove, Roswell Eldridge, Dilys M Parry, James F Gusella
PMCID: PMC1918355  PMID: 7913580

Abstract

Neurofibromatosis 2 (NF2) is a genetic disorder characterized by the development of multiple nervous-system tumors in young adulthood. The NF2 gene has recently been isolated and found to encode a new member of the protein 4.1 family of cytoskeletal associated proteins, which we have named merlin. To define the molecular basis of NF2 in affected individuals, we have used SSCP analysis to scan the exons of the NF2 gene from 33 unrelated patients with NF2. Twenty unique SSCP variants were seen in 21 patients; 10 of these individuals were known to be the only affected person in their kindred, while 7 had at least one other known affected relative. In all cases in which family members were available, the SSCP variant segregated with the disease; comparison of sporadic cases with their parents confirmed the de novo variants. DNA sequence analysis revealed that 19 of the 20 variants observed are predicted to lead to a truncated protein due to frameshift, creation of a stop codon, or interference with normal RNA splicing. A single patient carried a 3-bp deletion removing a phenylalanine residue. We conclude that the majority of NF2 patients carry an inactivating mutation of the NF2 gene and that neutral polymorphism in the gene is rare.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson M. A., Gusella J. F. Use of cyclosporin A in establishing Epstein-Barr virus-transformed human lymphoblastoid cell lines. In Vitro. 1984 Nov;20(11):856–858. doi: 10.1007/BF02619631. [DOI] [PubMed] [Google Scholar]
  2. Bianchi A. B., Hara T., Ramesh V., Gao J., Klein-Szanto A. J., Morin F., Menon A. G., Trofatter J. A., Gusella J. F., Seizinger B. R. Mutations in transcript isoforms of the neurofibromatosis 2 gene in multiple human tumour types. Nat Genet. 1994 Feb;6(2):185–192. doi: 10.1038/ng0294-185. [DOI] [PubMed] [Google Scholar]
  3. Evans D. G., Huson S. M., Donnai D., Neary W., Blair V., Newton V., Harris R. A clinical study of type 2 neurofibromatosis. Q J Med. 1992 Aug;84(304):603–618. [PubMed] [Google Scholar]
  4. Haase V. H., Trofatter J. A., MacCollin M., Tarttelin E., Gusella J. F., Ramesh V. The murine NF2 homologue encodes a highly conserved merlin protein with alternative forms. Hum Mol Genet. 1994 Mar;3(3):407–411. doi: 10.1093/hmg/3.3.407. [DOI] [PubMed] [Google Scholar]
  5. Irving R. M., Moffat D. A., Hardy D. G., Barton D. E., Xuereb J. H., Maher E. R. Somatic NF2 gene mutations in familial and non-familial vestibular schwannoma. Hum Mol Genet. 1994 Feb;3(2):347–350. doi: 10.1093/hmg/3.2.347. [DOI] [PubMed] [Google Scholar]
  6. Jacoby L. B., MacCollin M., Louis D. N., Mohney T., Rubio M. P., Pulaski K., Trofatter J. A., Kley N., Seizinger B., Ramesh V. Exon scanning for mutation of the NF2 gene in schwannomas. Hum Mol Genet. 1994 Mar;3(3):413–419. doi: 10.1093/hmg/3.3.413. [DOI] [PubMed] [Google Scholar]
  7. MacCollin M., Mohney T., Trofatter J., Wertelecki W., Ramesh V., Gusella J. DNA diagnosis of neurofibromatosis 2. Altered coding sequence of the merlin tumor suppressor in an extended pedigree. JAMA. 1993 Nov 17;270(19):2316–2320. doi: 10.1001/jama.270.19.2316. [DOI] [PubMed] [Google Scholar]
  8. Martuza R. L., Eldridge R. Neurofibromatosis 2 (bilateral acoustic neurofibromatosis). N Engl J Med. 1988 Mar 17;318(11):684–688. doi: 10.1056/NEJM198803173181106. [DOI] [PubMed] [Google Scholar]
  9. Mulvihill J. J., Parry D. M., Sherman J. L., Pikus A., Kaiser-Kupfer M. I., Eldridge R. NIH conference. Neurofibromatosis 1 (Recklinghausen disease) and neurofibromatosis 2 (bilateral acoustic neurofibromatosis). An update. Ann Intern Med. 1990 Jul 1;113(1):39–52. doi: 10.7326/0003-4819-113-1-39. [DOI] [PubMed] [Google Scholar]
  10. Narod S. A., Parry D. M., Parboosingh J., Lenoir G. M., Ruttledge M., Fischer G., Eldridge R., Martuza R. L., Frontali M., Haines J. Neurofibromatosis type 2 appears to be a genetically homogeneous disease. Am J Hum Genet. 1992 Sep;51(3):486–496. [PMC free article] [PubMed] [Google Scholar]
  11. Orita M., Suzuki Y., Sekiya T., Hayashi K. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics. 1989 Nov;5(4):874–879. doi: 10.1016/0888-7543(89)90129-8. [DOI] [PubMed] [Google Scholar]
  12. Rouleau G. A., Merel P., Lutchman M., Sanson M., Zucman J., Marineau C., Hoang-Xuan K., Demczuk S., Desmaze C., Plougastel B. Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2. Nature. 1993 Jun 10;363(6429):515–521. doi: 10.1038/363515a0. [DOI] [PubMed] [Google Scholar]
  13. Rubio M. P., Correa K. M., Ramesh V., MacCollin M. M., Jacoby L. B., von Deimling A., Gusella J. F., Louis D. N. Analysis of the neurofibromatosis 2 gene in human ependymomas and astrocytomas. Cancer Res. 1994 Jan 1;54(1):45–47. [PubMed] [Google Scholar]
  14. Ruttledge M. H., Sarrazin J., Rangaratnam S., Phelan C. M., Twist E., Merel P., Delattre O., Thomas G., Nordenskjöld M., Collins V. P. Evidence for the complete inactivation of the NF2 gene in the majority of sporadic meningiomas. Nat Genet. 1994 Feb;6(2):180–184. doi: 10.1038/ng0294-180. [DOI] [PubMed] [Google Scholar]
  15. Trofatter J. A., MacCollin M. M., Rutter J. L., Murrell J. R., Duyao M. P., Parry D. M., Eldridge R., Kley N., Menon A. G., Pulaski K. A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell. 1993 Mar 12;72(5):791–800. doi: 10.1016/0092-8674(93)90406-g. [DOI] [PubMed] [Google Scholar]
  16. Trofatter J. A., MacCollin M. M., Rutter J. L., Murrell J. R., Duyao M. P., Parry D. M., Eldridge R., Kley N., Menon A. G., Pulaski K. A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell. 1993 Nov 19;75(4):826–826. doi: 10.1016/0092-8674(93)90501-g. [DOI] [PubMed] [Google Scholar]
  17. Twist E. C., Ruttledge M. H., Rousseau M., Sanson M., Papi L., Merel P., Delattre O., Thomas G., Rouleau G. A. The neurofibromatosis type 2 gene is inactivated in schwannomas. Hum Mol Genet. 1994 Jan;3(1):147–151. doi: 10.1093/hmg/3.1.147. [DOI] [PubMed] [Google Scholar]

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