A genetic study of type 2 neurofibromatosis in the United Kingdom. I. Prevalence, mutation rate, fitness, and confirmation of maternal transmission effect on severity.

Evans, D. Gareth; Huson, Susan M.; Donnai, Dian; Neary, Wanda; Blair, Vilray P.; Teare, Dawn; Newton, Valerie; Strachan, Tom; Ramsden, R. T.; Harris, Rodney

doi:10.1136/jmg.29.12.841

Cited by 440 publications

(249 citation statements)

References 17 publications

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“…Insights into the genetic aetiology of meningioma have derived from the study of individuals with the inherited cancer predisposition syndrome neurofibromatosis type 2 (NF2), in which 50% of affected individuals develop meningioma (Evans et al, 1992). The central role of the NF2 gene in regulating leptomeningeal cell proliferation is underscored by the finding of biallelic NF2 gene inactivation in 50-80% of sporadic meningiomas (Ruttledge et al, 1994;Gutmann et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Identification of a progenitor cell of origin capable of generating diverse meningioma histological subtypes

et al. 2011

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Meningiomas are among the most common primary central nervous system tumours in adults. Studies focused on the molecular basis for meningioma development are hampered by a lack of information with regard to the cell of origin for these brain tumours. Herein, we identify a prostaglandin D synthase-positive meningeal precursor as the cell of origin for murine meningioma, and show that neurofibromatosis type 2 (Nf2) inactivation in prostaglandin D2 synthase (PGDS) ( þ ) primordial meningeal cells, before the formation of the three meningeal layers, accounts for the heterogeneity of meningioma histological subtypes. Using a unique PGDSCre strain, we define a critical embryonic and early postnatal developmental window in which biallelic Nf2 inactivation in PGDS ( þ ) progenitor cells results in meningioma formation. Moreover, we identify differentially expressed markers that characterize the two major histological meningioma subtypes both in human and mouse tumours. Collectively, these findings establish the cell of origin for these common brain tumours as well as a susceptible developmental period in which signature genetic mutations culminate in meningioma formation.

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Section: Introductionmentioning

confidence: 99%

Identification of a progenitor cell of origin capable of generating diverse meningioma histological subtypes

et al. 2011

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“…For these patients, there exists the auditory brainstem implant (ABI), which stimulates the surface of the cochlear nucleus. The initial motivation for the ABI was to restore hearing in neurofibromatosis type II (NF2) patients [ϳ1 in 40,000 births (Evans et al, 1992)], who usually develop bilateral acoustic neuromas and require tumor removal that leads to complete deafness. Because the cochlear nucleus is approached during tumor surgery, it was selected as the implant site.…”

Section: Introductionmentioning

confidence: 99%

Electrical Stimulation of the Midbrain for Hearing Restoration: Insight into the Functional Organization of the Human Central Auditory System

Lim¹,

Lenarz²,

Joseph³

et al. 2007

J. Neurosci.

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The cochlear implant can restore speech perception in patients with sensorineural hearing loss. However, it is ineffective for those without an implantable cochlea or a functional auditory nerve. These patients can be implanted with the auditory brainstem implant (ABI), which stimulates the surface of the cochlear nucleus. Unfortunately, the ABI has achieved limited success in its main patient group [i.e., those with neurofibromatosis type 2 (NF2)] and requires a difficult surgical procedure. These limitations have motivated us to develop a new hearing prosthesis that stimulates the midbrain with a penetrating electrode array. We recently implanted three patients with the auditory midbrain implant (AMI), and it has proven to be safe with minimal movement over time. The AMI provides loudness, pitch, temporal, and directional cues, features that have shown to be important for speech perception and more complex sound processing. Thus far, all three patients obtain enhancements in lip reading capabilities and environmental awareness and some improvements in speech perception comparable with that of NF2 ABI patients. Considering that our midbrain target is more surgically exposable than the cochlear nucleus, this argues for the use of the AMI as an alternative to the ABI. Fortunately, we were able to stimulate different midbrain regions in our patients and investigate the functional organization of the human central auditory system. These findings provide some insight into how we may need to stimulate the midbrain to improve hearing performance with the AMI.

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“…Merlin (or schwannomin) is a tumor suppressor protein for neuro®bromatosis type-2, an autosomal dominant disease, which is characterized by the development of bilateral vestibular Schwann cell tumors (schwannomas), meningiomas, spinal shwannomas, and/or subcapsular lens opacities (Martuza and Eldridge, 1988;Evans et al, 1992). Antisense suppression of merlin expression results in inhibition of cell adhesion as well as an increase in proliferation in culture (Huynh and Pulst, 1996).…”

Section: Introductionmentioning

confidence: 99%

Expression level, subcellular distribution and Rho-GDI binding affinity of merlin in comparison with ezrin/radixin/moesin proteins

et al. 1999

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Merlin, a neuro®bromatosis type-2 tumor suppressor, shows signi®cant sequence similarity to ERM (Ezrin/ Radixin/Moesin) proteins, general actin ®lament/plasma membrane cross-linkers, which are regulated in a Rhodependent manner. To understand its physiological functions, we compared merlin with ERM proteins in vivo and in vitro. Quantitative immunoblotting revealed that the molar ratio of merlin/ERM in cultured epithelial or non-epithelial cells was *0.14 or *0.05, respectively. After centrifugation of cell homogenate, merlin was mostly recovered in the insoluble fraction, whereas almost half of ERM proteins were found in the soluble fraction. Merlin and ERM proteins were concentrated at microvilli when introduced into ®broblasts. In contrast, in epithelial cells, introduced merlin was co-distributed with E-cadherin in lateral membranes, whereas ERM proteins were concentrated in apical microvilli. Finally, we examined the binding anity of merlin to Rho GDP dissociation inhibitor (Rho-GDI), to which N-terminal halves of ERM proteins but not the full-length molecules speci®cally bind. In vitro binding assays revealed that the N-terminal halves of merlin isoform-I and -II as well as full-length merlin isoform-II bound to Rho-GDI with similar binding anity to ERM proteins. Immunoprecipitation con®rmed these ®ndings in vivo. These ®ndings do not favor the notion that merlin functions simply in a redundant or competitive manner to ERM proteins.

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A genetic study of type 2 neurofibromatosis in the United Kingdom. I. Prevalence, mutation rate, fitness, and confirmation of maternal transmission effect on severity.

Cited by 440 publications

References 17 publications

Identification of a progenitor cell of origin capable of generating diverse meningioma histological subtypes

Identification of a progenitor cell of origin capable of generating diverse meningioma histological subtypes

Electrical Stimulation of the Midbrain for Hearing Restoration: Insight into the Functional Organization of the Human Central Auditory System

Expression level, subcellular distribution and Rho-GDI binding affinity of merlin in comparison with ezrin/radixin/moesin proteins

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