Germline screening of the NF-2 gene in families with unilateral vestibular schwannoma

Ph, Bikhazi; Ak, Lalwani; Ej, Kim; Bikhazi, Nadim B.; Attaie, Ali; Wh, Slattery; Rk, Jackler; De, Brackmann

doi:10.1016/s0194-5998(97)80072-1

Cited by 4 publications

(2 citation statements)

References 14 publications

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“…It may be more likely that individuals in affected families have an alternative genetic cause altogether. In one study by Bikhazi et al (22), six families underwent germline NF2 mutation screening because each pedigree had two affected individuals. Because none had a germline NF2 mutation, the authors concluded that either a coincidental NF2 somatic mutation occurred in multiple individuals or alternative genetic loci may be responsible.…”

Section: Discussionmentioning

confidence: 99%

Is There an Inherited Contribution to Risk for Sporadic Unilateral Vestibular Schwannoma? Evidence of Familial Clustering

et al. 2022

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Object: Unlike the autosomal dominant inheritance of neurofibromatosis 2, there are no known inherited risk factors for sporadic, unilateral vestibular schwannoma (VS), which comprise most VS cases. The authors tested a hypothesis positing a genetic contribution to predisposition to these lesions by analyzing familial clustering of cases. Methods: Familial clustering of individuals with unilateral VS was analyzed in two independent genealogical resources with linked diagnosis data: the Veterans Health Administration Genealogy Resource and the Utah Population Database. Tests for excess relatedness, estimation of relative risks (RRs) in close and distant relatives, and identification of pedigrees with a significant excess of unilateral VS among descendants were performed. Results: The average pairwise relatedness of the Veterans Health Administration Genealogy Resource VS cases significantly exceeded the expected relatedness ( p = 0.016), even when close relationships were ignored ( p = 0.002). RR for third-and fifth-degree relatives developing VS were significantly elevated (RR, 60.83; p = 0.0005; 95% confidence interval [CI], 7.37-219.73) and (RR, 11.88; p = 0.013; 95% CI, 1.44-42.90), respectively. No VS-affected first-, second-, or fourth-degree relatives were observed. In the Utah Population Database population, no first-or second-degree relatives with VS were observed. RR for fifth-degree relatives developing VS was significantly elevated (RR, 2.23; p = 0.009; 95% CI, 1.15-3.90). Conclusion: These results provide strong evidence for an inherited predisposition to sporadic, unilateral VS. This study exhibits the value of genealogical resources with linked medical data for examining hypotheses regarding inherited predisposition. The high-risk unilateral VS pedigrees identified in two independent resources provide a powerful means of pursuing predisposition gene identification.

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Section: Discussionmentioning

confidence: 99%

Is There an Inherited Contribution to Risk for Sporadic Unilateral Vestibular Schwannoma? Evidence of Familial Clustering

et al. 2022

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“…The loss of chromosome 22q in up to 45% of sporadic VSs strongly implicates a shared genetic pathogenesis with NF2-associated schwannomas. 5 The NF2 gene mutation and loss of merlin production have also been observed in sporadic VS tissue. 21 This finding strongly argues for the NF2 gene as a critical regulator of Schwann cell growth, with inactivation of the NF2 gene being an essential step in tumorigenesis.…”

Section: Nf2 Mutations Identified In Sporadic Vssmentioning

confidence: 99%

Molecular biology of familial and sporadic vestibular schwannomas: implications for novel therapeutics

Sughrue

Yeung²,

Rutkowski

et al. 2011

JNS

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Vestibular schwannomas (VSs) are benign tumors arising from the sheath of cranial nerve VIII. The pathogenesis underlying most familial and sporadic VSs has been linked to a mutation in a single gene, the neurofibromin 2 (NF2) gene located on chromosome 22, band q11-13.1. In this review, the authors summarized what is known about the epidemiology of NF2 mutations and patients with VSs. The authors also discuss the function of the NF2 gene product, merlin, and describe the known and hypothetical effects of genetic mutations that lead to merlin dysfunction on a broad variety of cellular and histological end points. A better understanding of the molecular pathobiology of VSs may lead to novel therapeutics to augment current modalities of treatment while minimizing morbidity.

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The association of NF2 (neurofibromin 2) gene polymorphism and the risk of medulloblastomas

Zhao

Chen

et al. 2018

Neurol Sci

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To explore the relationship between NF2 promoter gene mutation and the risk of medulloblastomas (MBs). We collected tissues from 16 MB patients and 7 age-matched non-MB controls. Gene sequencing, qPCR (real-time quantitative polymerase chain reaction), IHC (immunohistochemistry), and WB (Western blot) were used to analyze the changes in the NF2 gene sequence and expression between patients and controls. We found that NF2 promoter gene mutations occurred in MB patients. The NF2 mRNA expression was higher in the controls than in patients (p = 0.03 < 0.05); however, the results of IHC and WB demonstrated that the NF2 protein expression was significantly higher in patients than in the controls (IHC: p = 0.0001; WB: p = 0.01). There was no significant difference in the CRL4 mRNA and protein levels. In addition, NF2 protein was mainly expressed in the nucleus in MB patients, while the NF2 protein was mainly expressed in the cytoplasm in the controls. NF2 promoter mutations exist in MB patients. NF2 mRNA expression was higher in controls than patients; whereas NF2 protein level was higher in patients than in controls.

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Germline screening of the NF-2 gene in families with unilateral vestibular schwannoma

Cited by 4 publications

References 14 publications

Is There an Inherited Contribution to Risk for Sporadic Unilateral Vestibular Schwannoma? Evidence of Familial Clustering

Is There an Inherited Contribution to Risk for Sporadic Unilateral Vestibular Schwannoma? Evidence of Familial Clustering

Molecular biology of familial and sporadic vestibular schwannomas: implications for novel therapeutics

The association of NF2 (neurofibromin 2) gene polymorphism and the risk of medulloblastomas

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