Molecular Analysis of the NF2 Tumor-suppressor Gene in Schwannomatosis

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 1997 Dec 18

PMID 9399891

Citations 43

Authors

L B Jacoby

D Jones

K Davis

D Kronn

M P Short

J Gusella

M Maccollin

Affiliations

Soon will be listed here.

Abstract

Patients with multiple schwannomas without vestibular schwannomas have been postulated to compose a distinct subclass of neurofibromatosis (NF), termed "schwannomatosis." To compare the molecular-genetic basis of schwannomatosis with NF2, we examined the NF2 locus in 20 unrelated schwannomatosis patients and their affected relatives. Tumors from these patients frequently harbored typical truncating mutations of the NF2 gene and loss of heterozygosity of the surrounding region of chromosome 22. Surprisingly, unlike patients with NF2, no heterozygous NF2-gene changes were seen in normal tissues. Examination of multiple tumors from the same patient revealed that some schwannomatosis patients are somatic mosaics for NF2-gene changes. By contrast, other individuals, particularly those with a positive family history, appear to have an inherited predisposition to formation of tumors that carry somatic alterations of the NF2 gene. Further work is needed to define the pathogenetics of this unusual disease mechanism.

Citing Articles

Multiple schwannomas of cauda equina and peripherals: A case report.

Chen Q, Yuan H, Zhao Y, Zhou K Radiol Case Rep. 2024; 19(11):5424-5428.

PMID: 39285972 PMC: 11403415. DOI: 10.1016/j.radcr.2024.08.047.

Historical Development of Diagnostic Criteria for NF2-related Schwannomatosis.

Tamura R, Yo M, Toda M Neurol Med Chir (Tokyo). 2024; 64(8):299-308.

PMID: 38897938 PMC: 11374461. DOI: 10.2176/jns-nmc.2024-0067.

Managing Multiple Schwannomatosis of Vagus and Hypoglossal Nerves: The Unanticipated Complications.

Verma N, Yadav M, Yadav G, Arya S Indian J Otolaryngol Head Neck Surg. 2023; 75(2):1162-1168.

PMID: 37275115 PMC: 10235340. DOI: 10.1007/s12070-022-03460-z.

Rare Diseases of the Oral Cavity, Neck, and Pharynx.

Reichel C Laryngorhinootologie. 2021; 100(S 01):S1-S24.

PMID: 34352905 PMC: 8432966. DOI: 10.1055/a-1331-2851.

A rare case of schwannomatosis of the extremities.

Fodor L, Samuila S, Bodog F J Int Med Res. 2020; 48(9):300060520952278.

PMID: 32938291 PMC: 7503024. DOI: 10.1177/0300060520952278.

References

LEWIS Jr R, NANNINI L, COCKE Jr W . Multifocal neurilemmomas of median and ulnar nerves of the same extremity--case report. J Hand Surg Am. 1981; 6(4):406-8. DOI: 10.1016/s0363-5023(81)80054-8. View

SHISHIBA T, Niimura M, Ohtsuka F, Tsuru N . Multiple cutaneous neurilemmomas as a skin manifestation of neurilemmomatosis. J Am Acad Dermatol. 1984; 10(5 Pt 1):744-54. DOI: 10.1016/s0190-9622(84)70089-2. View

Anderson M, Gusella J . Use of cyclosporin A in establishing Epstein-Barr virus-transformed human lymphoblastoid cell lines. In Vitro. 1984; 20(11):856-8. DOI: 10.1007/BF02619631. View

Berger T, Lapins N, ENGEL M . Agminated neurilemomas. J Am Acad Dermatol. 1987; 17(5 Pt 2):891-4. DOI: 10.1016/s0190-9622(87)70276-x. View

Purcell S, Dixon S . Schwannomatosis. An unusual variant of neurofibromatosis or a distinct clinical entity?. Arch Dermatol. 1989; 125(3):390-3. DOI: 10.1001/archderm.125.3.390. View

Freidlin V, Datiles M, Edwards P, Sherman J, Parry D, McCain L . The association of posterior capsular lens opacities with bilateral acoustic neuromas in patients with neurofibromatosis type 2. Arch Ophthalmol. 1989; 107(4):541-4. DOI: 10.1001/archopht.1989.01070010555030. View

Sasaki T, Nakajima H . Congenital neurilemmomatosis. J Am Acad Dermatol. 1992; 26(5 Pt 1):786-7. DOI: 10.1016/s0190-9622(08)80565-8. View

Weissenbach J, Gyapay G, Dib C, Vignal A, Morissette J, Millasseau P . A second-generation linkage map of the human genome. Nature. 1992; 359(6398):794-801. DOI: 10.1038/359794a0. View

Buenger K, Porter N, Dozier S, Wagner Jr R . Localized multiple neurilemmomas of the lower extremity. Cutis. 1993; 51(1):36-8. View

10.

Evans D, Huson S, Donnai D, Neary W, Blair V, Newton V . A clinical study of type 2 neurofibromatosis. Q J Med. 1992; 84(304):603-18. View

11.

Bouzas E, Parry D, Eldridge R . Visual impairment in patients with neurofibromatosis 2. Neurology. 1993; 43(3 Pt 1):622-3. DOI: 10.1212/wnl.43.3_part_1.622. View

12.

Trofatter J, MacCollin M, Rutter J, Murrell J, Duyao M, Parry D . A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell. 1993; 72(5):791-800. DOI: 10.1016/0092-8674(93)90406-g. View

13.

Marineau C, Baron C, Delattre O, ZUCMAN J, Thomas G, Rouleau G . Dinucleotide repeat polymorphism at the D22S268 locus. Hum Mol Genet. 1993; 2(3):336. DOI: 10.1093/hmg/2.3.336-a. View

14.

Rouleau G, Merel P, Lutchman M, Sanson M, ZUCMAN J, Marineau C . Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2. Nature. 1993; 363(6429):515-21. DOI: 10.1038/363515a0. View

15.

Mautner V, Tatagiba M, Guthoff R, Samii M, Pulst S . Neurofibromatosis 2 in the pediatric age group. Neurosurgery. 1993; 33(1):92-6. DOI: 10.1227/00006123-199307000-00014. View

16.

Sainz J, Nechiporuk A, Kim U, Simon M, Pulst S . CA-repeat polymorphism at the D22S430 locus adjacent to NF2. Hum Mol Genet. 1993; 2(12):2203. DOI: 10.1093/hmg/2.12.2203. View

17.

Arpin M, Algrain M, Louvard D . Membrane-actin microfilament connections: an increasing diversity of players related to band 4.1. Curr Opin Cell Biol. 1994; 6(1):136-41. DOI: 10.1016/0955-0674(94)90127-9. View

18.

Jacoby L, Maccollin M, Louis D, Mohney T, Rubio M, Pulaski K . Exon scanning for mutation of the NF2 gene in schwannomas. Hum Mol Genet. 1994; 3(3):413-9. DOI: 10.1093/hmg/3.3.413. View

19.

Maccollin M, Ramesh V, Jacoby L, Louis D, Rubio M, Pulaski K . Mutational analysis of patients with neurofibromatosis 2. Am J Hum Genet. 1994; 55(2):314-20. PMC: 1918355. View

20.

Honda M, Arai E, Sawada S, Ohta A, Niimura M . Neurofibromatosis 2 and neurilemmomatosis gene are identical. J Invest Dermatol. 1995; 104(1):74-7. DOI: 10.1111/1523-1747.ep12613537. View