National Cancer Institute®
Last Modified: January 1, 2002
UI - 11448944
AU - Gutmann DH; Hirbe AC; Haipek CA
TI - Functional analysis of neurofibromatosis 2 (NF2) missense mutations.
SO - Hum Mol Genet 2001 Jul 1;10(14):1519-29
AD - Department of Neurology, Washington University School of Medicine, Box 8111, 660 South Euclid Avenue, St Louis, MO 63110, USA. firstname.lastname@example.org
Neurofibromatosis 2 (NF2) is a tumor predisposition syndrome in which affected individuals develop nervous system tumors at an increased frequency. The most common tumor in individuals with NF2 is the schwannoma, which is composed of neoplastic Schwann cells lacking NF2 gene expression. Moreover, inactivation of the NF2 gene is observed in nearly all sporadic schwannomas, suggesting that the NF2 gene is a critical growth regulator for Schwann cells. In an effort to gain insights into the function of the NF2 gene product, merlin or schwannomin, we performed a detailed functional analysis of eight naturally occurring non-conservative missense mutations in the NF2 gene. Using a regulatable expression system in rat schwannoma cells, we analyzed proliferation, actin cytoskeleton-mediated events and merlin folding. In this report, we demonstrate that mutations clustered in the predicted alpha-helical region did not impair the function of merlin whereas those in either the N- or C-terminus of the protein rendered merlin inactive as a negative growth regulator. These results suggest that the key functional domains of merlin lie within the highly conserved FERM domain and the unique C-terminus of the protein.
UI - 11706558
AU - Ishii S; Han S; Shiiba K; Mizoi T; Okabe M; Horii A; Nagura H; Matsuno
TI - S; Sasaki I Allelic loss of the NF1 gene in anal malignant melanoma in a patient with neurofibromatosis type 1.
SO - Int J Clin Oncol 2001 Aug;6(4):201-4
AD - Division of Biological Regulation and Oncology, Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aoba-ku, Sendai 980-8574, Japan. email@example.com
A 64-year-old man with neurofibromatosis type 1 (NF1) developed a primary malignant melanoma of the anus. Genetic analysis of the resected tumor confirmed loss of heterozygosity (LOH) of the NF1 gene. Anorectal malignant melanoma in NF1 is extremely rare, and genetic studies of the NF1 gene in such patients have not been reported. The allelic loss detected in the present patient supports the previously raised idea that NF1 can function as a tumor suppressor gene in the development of malignant melanoma in patients with NF1.
UI - 11701400
AU - Kaufmann D; Tinschert S; Algermissen B
TI - Is the distribution of dermal neurofibromas in neurofibromatosis type 1 (NF1) related to the pattern of the skin surface temperature?
SO - Eur J Dermatol 2001 Nov-Dec;11(6):521-6
AD - Abteilung Humangenetik, Universitat Ulm, Albert-Einstein-Allee 11, D 89070 Ulm, Germany. firstname.lastname@example.org
The formation of dermal neurofibromas is a hallmark of the neurofibromatosis type 1 (NF1). A total loss of the NF1 gene product by stochastic events inactivating the wild type allele in Schwann cells should precede the development of neurofibromas. Dermal neurofibromas tend to be located mainly on the surface of the trunk and not in the body periphery. This distribution partly resembles the density of sensitive nerve endings in the epidermis. Our hypothesis is that a better correlation concerns the pattern of normal body surface temperature. According to our clinical observations we assume that in skin areas with higher temperatures the number of visible dermal neurofibromas is higher than in colder areas such as the arms/legs or nose. It is known that differences in temperature are able to determine differentiation. We suggest that the regulation of skin temperature is also involved in the formation of NF1 dermal neurofibromas and is related to the intrafamilial variability in NF1.
UI - 11727613
AU - Kros JM; Wolbers JG
TI - [Meningiomas: prognostic relevance of histopathologic and genetic markers]
SO - Ned Tijdschr Geneeskd 2001 Nov 10;145(45):2160-5
AD - Afd. Pathologie, Erasmus Universitair Medisch Centrum, Postbus 2040, 3000 CA Rotterdam. email@example.com
The majority of meningiomas are histologically benign tumours. Location and invasion of tumour tissue in adjacent structures may hamper radical resections and give rise to recurrences. The rise in human life expectancy has prolonged the postoperative period and thus the risk of tumour recurrence has increased markedly. Infiltration in brain tissue and mitotic activity are important histologic features which negatively influence the disease-free duration of the postoperative period. Molecular studies of relevant genetic defects involved in meningioma are currently underway, but as yet these are of little clinical relevance.
UI - 11727265
AU - Sakamoto A; Oda Y; Oshiro Y; Tamiya S; Iwamoto Y; Tsuneyoshi M
TI - Immunoexpression of neurofibromin, S-100 protein, and leu-7 and mutation analysis of the NF1 gene at codon 1423 in osteofibrous dysplasia.
SO - Hum Pathol 2001 Nov;32(11):1245-51
AD - Department of Anatomic Pathology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
The NF1 (neurofibromatosis type 1, or von Recklinghausen disease) gene, is a tumor-suppressor gene, and its product, neurofibromin, down-regulates ras protein by its guanosine triphosphatase-activating protein (GAP)-related domain. Osteofibrous dysplasia (OFD) is characterized by fibroblast-like spindle cells and osseous tissue and is generally seen in the tibia or fibula during childhood. The precise nature of OFD remains controversial. Cosegregations of OFD and NF1 have been reported, and it has been surmised that OFD is associated with the NF1 gene. We studied the expressions of NF1 gene product (neurofibromin) and so-called Schwann cell markers (S-100 protein, Leu-7) in 17 cases of OFD immunohistochemically. Ten cases of fibrous dysplasia (FD) were also used for the purpose of comparison. Five OFD and 7 FD cases were analyzed for NF1 gene mutation at codon 1423, which is a GAP-related domain, by single-strand conformation polymorphism. Fibroblast-like cells of OFD showed the expression of neurofibromin (5 of 17), S-100 protein (9 of 17), and Leu-7 (5 of 17), and those of FD did not show these expressions, with the exception of 1 case that showed Leu-7 expression. Regarding the OFD cases, significant correspondence was found between cases showing expression of neurofibromin and S-100 protein, between cases showing expression of neurofibromin and Leu-7, and between cases showing expression of S-100 protein and Leu-7 (P < .01). NF1 gene mutation at codon 1423 was not detected in either the OFD (0 of 5) or FD (0 of 7) cases. These results seem to suggest the possible involvement of neurofibromin in the development of OFD, which is associated with the expression of Schwann cell markers (S-100 protein and Leu-7). Furthermore, NF1 gene mutation at codon 1423 did not seem to be related to OFD. Copyright 2001 by W.B. Saunders Company
UI - 11735023
AU - Han SS; Cooper DN; Upadhyaya MN
TI - Evaluation of denaturing high performance liquid chromatography (DHPLC) for the mutational analysis of the neurofibromatosis type 1 ( NF1) gene.
SO - Hum Genet 2001 Nov;109(5):487-97
AD - Institute of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UK.
The identification of mutations in the NF1 gene causing type 1 neurofibromatosis (NF1) has presented a considerable challenge because of the large size of the gene, the lack of significant mutational clustering, the diversity of the underlying pathological lesions and the presence of NF1 pseudogenes. Denaturing high performance liquid chromatography (DHPLC), a high throughput, non-hazardous and largely automated heteroduplex-based technique, is in many ways ideally suited to mutation detection in this condition. DHPLC was therefore optimised for the rapid screening of the 60 exons and splice junctions of the NF1 gene in patients with NF1. The sensitivity of DHPLC was evaluated in a retrospective study of a cohort of 111 unrelated NF1 patients with known germline mutations; 97% of mutations were detected. In a subsequent prospective analysis of 50 unrelated NF1 patients, germline mutations were identified in 34 individuals (68%), 22 of these alterations being novel. This represents the highest rate of mutation detection so far reported for the NF1 gene with a single screening technique and genomic DNA as a target.
UI - 11729745
AU - Rudolph G; Haritoglou C; Kalpadakis P; Boergen KP; Meitinger T
TI - [LEOPARD syndrome with iris-retina-choroid coloboma. Discordant findings in monozygotic twins (MIM # 151 100)]
SO - Ophthalmologe 2001 Nov;98(11):1101-3
AD - Augenklinik, Ludwig-Maximilians-Universitat Munchen, Mathildenstrasse 8, 80336 Munchen. Guenther.Rudolph@ak-i.med.uni-muenchen.de
INTRODUCTION: The LEOPARD syndrome is an autosomal dominant inherited disease with severe lentiginosis associated with various abnormalities such as electrocardiographic abnormalities, ocular hypertelorism, pulmonary stenosis, abnormalities of the genitalia, retardation of growth and deafness. Ocular manifestations such as coloboma of the iris, the retina and the choroid have not been reported so far. PATIENTS: We report the cases of two 10-year-old identical twins and their mother, showing typical manifestations consistent with the LEOPARD syndrome. Additionally, colobomas of the iris, the retina and the choroid were detected. RESULTS: In addition to the findings typical for the LEOPARD syndrome, we observed unusual ocular abnormalities in all three patients. It represents a discordant phenotype in monozygotic twins. CONCLUSION: LEOPARD syndrome is a disease with multiple alterations and abnormalities. Although ocular malformations seem to be rare, an ophthalmological examination is recommended in order to initiate early visual rehabilitation.
UI - 11765821
AU - Governale LS; Vortmeyer AO; Zhuang Z; Oldfield EH
TI - Fibrous meningioma in a patient with von Hippel-Lindau disease: a genetic analysis.
SO - J Neurosurg 2001 Dec;95(6):1045-9
AD - Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
Meningioma has been included in the constellation of tumors associated with von Hippel-Lindau (VHL) disease in previously published reports. It is unclear whether these tumors are an uncommon component of VHL disease or are more readily detected in these patients because of the frequency with which they undergo central nervous system imaging as part of the routine management of VHL disease. The authors report the case of a patient with VHL disease in whom a progressively enlarging supratentorial mass developed and was diagnosed as a hemangioblastoma because of its appearance on serial magnetic resonance images. At surgery the tumor displayed the typical features of a meningioma and was given the histological diagnosis of fibrous meningioma. Single-stranded conformational polymorphism analysis of the tumor DNA revealed a loss of heterozygosity at the neurofibromatosis Type 2 gene locus, known to be associated with sporadically occurring meningiomas. Despite this finding, the VHL gene locus on the allele from the patient's unaffected parent was normal. Thus it is unlikely that the occurrence of this patient's fibrous meningioma was associated with underlying VHL disease. Given the high frequency of neuroimaging sessions in patients with VHL disease, some supratentorial lesions that have been given radiological diagnoses of hemangioblastomas may be incidental meningiomas.
UI - 11565554
AU - Bahuau M; Pelet A; Vidaud D; Lamireau T; LeBail B; Munnich A; Vidaud M;
TI - Lyonnet S; Lacombe D GDNF as a candidate modifier in a type 1 neurofibromatosis (NF1) enteric phenotype.
SO - J Med Genet 2001 Sep;38(9):638-43
UI - 11704931
AU - Kaufmann D; Muller R; Bartelt B; Wolf M; Kunzi-Rapp K; Hanemann CO;
TI - Fahsold R; Hein C; Vogel W; Assum G Spinal neurofibromatosis without cafe-au-lait macules in two families with null mutations of the NF1 gene.
SO - Am J Hum Genet 2001 Dec;69(6):1395-400
AD - Departments of Human Genetics, University of Ulm, Ulm, Germany. firstname.lastname@example.org
Spinal neurofibromatosis (SNF) is considered to be an alternative form of neurofibromatosis, showing multiple spinal tumors and cafe-au-lait macules. Involvement of the neurofibromatosis type 1 (NF1) locus has been demonstrated, by linkage analysis, for three families with SNF. In one of them, a cosegregating frameshift mutation in exon 46 of the NF1 gene was identified. In the present study, we report four individuals from two families who carry NF1 null mutations that would be expected to cause NF1. Three patients have multiple spinal tumors and no cafe-au-lait macules, and the fourth has no clinical signs of NF1. In the first family, a missense mutation (Leu2067Pro) in NF1 exon 33 was found, and, in the second, a splice-site mutation (IVS31-5A-->G) enlarging exon 32 by 4 bp at the 5' end was found. The latter mutation has also been observed in an unrelated patient with classical NF1. Both NF1 mutations cause a reduction in neurofibromin of approximately 50%, with no truncated protein present in the cells. This demonstrates that typical NF1 null mutations can result in a phenotype that is distinct from classical NF1, showing only a small spectrum of the NF1 symptoms, such as multiple spinal tumors, but not completely fitting the current clinical criteria for SNF. We speculate that this phenotype is caused by an unknown modifying gene that compensates for some, but not all, of the effects caused by neurofibromin deficiency.
UI - 11754043
AU - Fang L; Chalhoub N; Li W; Feingold J; Ortenberg J; Lemieux B; Thirion JP
TI - Genotype analysis of the NF1 gene in the French Canadians from the Quebec population.
SO - Am J Med Genet 2001 Dec 1;104(3):189-98
AD - Departement de Microbiologie et d'Infectiologie, Faculte de Medecine, Universite de Sherbrooke, Sherbrooke, Quebec J1H 5N4, Canada.
We genotyped 19 NF1 families from the French Canadians of the Quebec population with six intragenic polymorphic markers including 2 RFLPs (EcoRI and RsaI) and 4 microsatellites (IVS26-2.3, IVS27AC28.4, IVS27AC33.1, and IVS38GT53.0). Genotype analysis indicated families 7610 and 7473 bear deletions. In Family 7610 the deletion removed the entire NF1 gene except exons 1 to 4b. The breakpoint of the deletion is located between exons 4a and 4b. The deletion 7473 was derived from the maternal chromosome and exons 1 to 5 were deleted. The breakpoint of the deletion is located between exons 7 and 13. Their phenotypes are reported. The allele frequencies of microsatellites IVS27AC28.4 and IVS38GT53.0 are compared to previously reported data from Caucasians, including Spanish and Italians. The difference is statistically significant (P < 0.0036) for marker IVS27AC28.4 between the Quebec French Canadian and the Italian population. Copyright 2001 Wiley-Liss, Inc.
UI - 2112353
AU - Mulvihill JJ; Parry DM; Sherman JL; Pikus A; Kaiser-Kupfer MI; Eldridge
TI - R NIH conference. Neurofibromatosis 1 (Recklinghausen disease) and neurofibromatosis 2 (bilateral acoustic neurofibromatosis). An update.
SO - Ann Intern Med 1990 Jul 1;113(1):39-52
AD - Department of Human Genetics, University of Pittsburgh, PA 15261.
The neurofibromatoses comprise at least two autosomal dominant disorders affecting an estimated 100,000 Americans with clinical manifestations that may require care from every type of clinician. Neurofibromatosis 1 and neurofibromatosis 2 have in common the occurrence of many neurofibromas but are distinctly different clinical disorders. The disease genes are on different chromosomes. Magnetic resonance imaging, particularly with gadolinium enhancement, has generally supplanted other techniques for visualizing brain, spinal, and other neural tumors in both disorders. The technique has rekindled the controversy over the nature and frequency of optic pathway tumors in patients with neurofibromatosis 1 and has revealed, throughout the brains of young patients, bright lesions that have uncertain clinical consequences and unknown pathologic bases. In patients with neurofibromatosis 2, small acoustic neuromas can be seen, leading to the possibility of excision with preservation of hearing and facial nerve function. Abnormal hearing may occur to excess in patients with neurofibromatosis 1, but acoustic neuroma has never been documented. In patients with neurofibromatosis 2, a battery of audiologic tests has a high positive predictive power. Lisch nodules or iris hamartomas, probably a universal sign in adults with the neurofibromatosis 1 gene, cause no problem with vision. Posterior capsular lens opacity in patients with neurofibromatosis 2 is a helpful diagnostic sign and a potential source of additional handicap in persons at risk for impaired hearing. Progress in the clinical delineation of the disorders has been matched with considerable research into the still obscure pathogenesis of the disorders. Such rapid advances may necessitate reconsideration of the conclusions of the National Institutes of Health Consensus Development Conference on Neurofibromatosis, especially those on the categories of persons in which a neurofibromatosis should be considered and the need for caution in recommending surgery. Watchful waiting may often be the best management for acoustic neuromas in neurofibromatosis 2.
UI - 2119939
AU - Andersen LB; Tommerup N; Koch J
TI - Formation of a minichromosome by excision of the proximal region of 17q in a patient with von Recklinghausen neurofibromatosis.
SO - Cytogenet Cell Genet 1990;53(4):206-10
AD - Institute of Medical Genetics, University of Copenhagen, Denmark.
An interstitial deletion, 17cen----q11.2 (or q12), and a small extra chromosome was found in a sporadic case of von Recklinghausen neurofibromatosis (NF1). In situ hybridization with a chromosome 17-specific alpha-satellite probe showed that the small chromosome was derived from the deleted region, most likely by an excision/ring formation. This chromosome rearrangement is in agreement with the localization of the von Recklinghausen neurofibromatosis (NF1) locus to the proximal region of 17q, but with a more distal breakpoint than observed in two previously described reciprocal translocations associated with NF1. If the NF1 gene has been truncated by the present rearrangement, it may suggest that the NF1 gene is a very large gene at the genomic level. Alternatively, NF1 in this patient may be caused by the gradual loss in somatic cells of the small chromosome carrying an intact NF1 gene, thereby suggesting a recessive mechanism at the gene level. Finally, an intact NF1 gene may have been placed in close proximity with alpha-satellite sequences, which might cause inactivation of the gene. The small supernumerary chromosome may not only facilitate the cloning of the NF1 gene itself, but also offers explanations of the mechanism underlying development of the disease.
UI - 1903909
AU - O'Connell P; Cawthon RM; Viskochil D; White R; Carey JC; Buchberg AM
TI - The NF1 translocation breakpoint region.
SO - Ann N Y Acad Sci 1991;615():319-31
AD - Howard Hughes Medical Institute, University of Utah Health Sciences Center, Salt Lake City 84132.
The genetic locus that harbors mutation(s) responsible for neurofibromatosis type 1 (NF1) is on chromosome 17, within band q11.2. We have mapped the human homologue of a murine gene (Evi-2) that is implicated in myeloid tumors, to a location between two NF1 translocation breakpoints on chromosome 17. Sequencing studies predict that EVI2 is a membrane protein that may complex with itself and/or other proteins within the membrane, perhaps to function as part of a cell-surface receptor. In the course of these studies we have also identified three other transcripts (classes of cDNAs) from the NF1 region. Two of them map between the NF1 translocation breakpoints; the remaining transcript maps just outside this region. The map location implicates these four genes as possible candidates for harboring NF1 mutations.
UI - 1723132
AU - Chan LC; Kwong YL; Ha SY
TI - Neurofibromatosis and increased risk of leukaemia--is the G-CSF gene involved?
SO - Leukemia 1991 Dec;5(12):1113-4
AD - Department of Pathology, Queen Mary Hospital, University of Hong Kong.
UI - 1424240
AU - Tommerup N; Warburg M; Gieselmann V; Hansen BR; Koch J; Petersen GB
TI - Ring chromosome 22 and neurofibromatosis.
SO - Clin Genet 1992 Oct;42(4):171-7
AD - Danish Center for Human Genome Research, Glostrup.
Variable constitutional mosaicism, mos45,XY,-22/46,XY,-22,+mar/46,XY,-22,+r(22)/47,XY,-22,+r(22)+mar/ 47, XY,-22,+r(22)*2, was found in PHA-stimulated peripheral blood, in a lymphoblastoid cell line and in cultured skin fibroblasts from a mentally retarded patient with neurofibromatosis. Both the ring chromosome and the small extra marker chromosome stained positively by in situ hybridization with a chromosome 14/22-specific alphoid repeat probe. DNA dosage analysis showed constitutional loss of one copy of the arylsulfatase A gene (ARSA), consistent with its terminal location on 22q. There was no evidence of constitutional loss of D22S1 or D22S28 which flank the neurofibromatosis type 2 (NF2) locus. Analysis of two DNA samples from a skin neurofibroma indicated retainment of two copies of D22S1, whereas the results were ambiguous with respect to tumor-specific loss of one copy of D22S28. It is suggested that the development of neurofibromatosis of unclear type in two r(22) carriers might be associated with somatic mutation of the NF2 locus due to instability of the ring chromosome(s), and in analogy, that somatic mutation of either NF1 or NF2 may account for some cases of neurofibromatosis which do not meet the criteria of either NF1 or NF2. The occurrence of seminoma in the proband may be fortuitous, but could also be due to the presence of a seminoma-associated locus on chromosome 22.
UI - 8418653
AU - Wiktor A; Van Dyke DL; Weiss L
TI - Characterization of a de novo 48,XX,+r(X),+r(17) by in situ hybridization in a patient with neurofibromatosis (NF1).
SO - Am J Med Genet 1993 Jan 1;45(1):22-4
AD - Medical Genetics and Birth Defects Center, Henry Ford Hospital, Detroit, Michigan 48202.
We describe a patient with familial neurofibromatosis (NF1), short stature, developmental delay, and a de novo chromosome abnormality. In situ hybridization was done using chromosome specific centromere probes to characterize the karyotype as 46,XX/47, XX,+r(X) (p11q11)/47,XX,+r(17) (p11q11)/48, XX,+r(X) (p11q11),+r(17) (p11q11). The NF1 mutation, as well as each supernumerary ring chromosome, may have played a role in perturbing the normal developmental process of this patient.
UI - 8453669
AU - Trofatter JA; MacCollin MM; Rutter JL; Murrell JR; Duyao MP; Parry DM;
TI - Eldridge R; Kley N; Menon AG; Pulaski K; et al A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor.
SO - Cell 1993 Mar 12;72(5):791-800
AD - Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown.
Neurofibromatosis 2 (NF2) is a dominantly inherited disorder characterized by the occurrence of bilateral vestibular schwannomas and other central nervous system tumors including multiple meningiomas. Genetic linkage studies and investigations of both sporadic and familial tumors suggest that NF2 is caused by inactivation of a tumor suppressor gene in chromosome 22q12. We have identified a candidate gene for the NF2 tumor suppressor that has suffered nonoverlapping deletions in DNA from two independent NF2 families and alterations in meningiomas from two unrelated NF2 patients. The candidate gene encodes a 587 amino acid protein with striking similarity to several members of a family of proteins proposed to link cytoskeletal components with proteins in the cell membrane. The NF2 gene may therefore constitute a novel class of tumor suppressor gene.
UI - 8374240
AU - Mautner VF; Hazim W; Guthoff R
TI - [Ophthalmologic differentiation of various forms of neurofibromatosis]
SO - Ophthalmologe 1993 Aug;90(4):391-3
AD - Neurologische Klinik, Allgemeines Krankenhaus Hamburg-Ochsenzoll.
Neurofibromatosis (NF) is one of the most frequent autosomal-dominant hereditary disorders. The molecular-genetic differentiation of NF 1 and NF 2 has important implications for the ophthalmologist. Among 80 patients with NF 1, Lisch nodules were diagnosed in 83% as typical criteria for the disease. In 6 patients who did not meet the NIH criteria for NF 1 and NF 2, the ophthalmological investigation showed no cataracts or Lisch nodules; thus, the ophthalmological examination can help to confirm a subtype of NF. In 8 out of 22 NF 2 patients a juvenile posterior subcapsular cataract was diagnosed. Our examination demonstrates that the diagnostic value of lens opacities in NF 2 patients--especially for early detection of the disease--must be clarified, especially with regard to the fact that there were no patients with incipient cataract and no neuroradiological criteria for the disease.
UI - 8228036
AU - Martinez-Lage JF; Poza M; Rodriguez Costa T
TI - Bilateral temporal arachnoid cysts in neurofibromatosis.
SO - J Child Neurol 1993 Oct;8(4):383-5
AD - Regional Service of Neurosurgery, Virgen de Arrixaca University Hospital, Murcia, Spain.
The occurrence of bilateral temporal arachnoid cysts has been considered as a rare event. Unilateral arachnoid pouches have been reported in a few instances associated with neurofibromatosis. The authors describe a 5-year-old girl with bilateral temporal arachnoid cysts who presented obvious stigmata of van Recklinghausen's disease. To the best of our knowledge, this is the first time that this association has been described in the literature.
UI - 8228039
AU - North K
TI - Neurofibromatosis type 1: review of the first 200 patients in an Australian clinic.
SO - J Child Neurol 1993 Oct;8(4):395-402
AD - Department of Neurology, Children's Hospital, Camperdown, Sydney, Australia.
Neurofibromatosis type 1 is a common multisystem disorder, best managed in a multidisciplinary clinic. In 1991, the first Australian neurofibromatosis clinic was established at the Children's Hospital, Camperdown, and the clinical characteristics of the first 150 families are reviewed. Two hundred individuals were assessed; there was an equal sex distribution, and 55% of cases were sporadic. Advanced paternal age appeared to predispose to new mutations in the neurofibromatosis gene. Cafe-au-lait spots and axillary freckling were important to the diagnosis of neurofibromatosis type 1 during childhood, and neurofibromas and Lisch nodules, although often not appearing until after puberty, were present in almost all patients over 30 years of age. Short stature (27%), macrocephaly (43%), scoliosis (20.5%), and learning disabilities (45%) were common associated features. The prevalence of disease complications was similar to the major US and European studies.
UI - 6786088
AU - Jennings MT; Bird TD
TI - Genetic influences in the epilepsies. Review of the literature with practical implications.
SO - Am J Dis Child 1981 May;135(5):450-7
We review hereditary influences in the epilepsies from the perspective of medical genetics. The recurrence risk for epilepsy in close relatives may vary from 2% to 5% up to 50% depending on the etiology of the seizure disorder in the proband. We emphasize the identification of specific disorders with single-gene inheritance that will lead to useful conclusions regarding treatment, prognosis, and family counseling. Also discussed are chromosomal aberrations, polygenic inheritance, gene-environment interactions, animal models of epilepsy, and the pharmacogenetics of anticonvulsants.
UI - 3084711
AU - Battersby RD; Ironside JW; Maltby EL
TI - Inherited multiple meningiomas: a clinical, pathological and cytogenetic study of an affected family.
SO - J Neurol Neurosurg Psychiatry 1986 Apr;49(4):362-8
The clinical features of a family with inherited multiple meningiomas as the major manifestation of neurofibromatosis are presented. The value of noninvasive radiological screening investigations is emphasised. The results of cytogenetic and pathological studies on the family are presented and discussed with a review of the relevant literature.
UI - 3119309
AU - Seizinger BR; Martuza RL; Rouleau G; Breakefield XO; Gusella JF
TI - Models for inherited susceptibility to cancer in the nervous system: a molecular-genetic approach to neurofibromatosis.
SO - Dev Neurosci 1987;9(3):144-53
AD - Neurogenetics Laboratory, Massachusetts General Hospital, Boston.
Neurofibromatosis (NF) is one of the most frequent and clinically important Mendelian disorders in man, with an incidence of 1 in 3,000. While different organ systems and cell types can be affected in NF, the most common abnormalities are in cells of neural crest origin. Two distinct forms of NF have been described: 'peripheral' or von Recklinghausen NF (VRNF) and 'central' or bilateral acoustic NF (BANF). VRNF is characterized clinically by hyperpigmented patches of skin and multiple tumors of the peripheral and central nervous system, which can cause disfigurement, paralysis, blindness and death. In comparison, BANF is characterized by the bilateral occurrence of acoustic neurinomas (Schwann cell-derived tumors of the 8th cranial nerve) and increased susceptibility to certain other nervous system tumors, including meningiomas and gliomas. These tumors can lead to deafness and other serious neurological morbidity and mortality within the first few decades of life. The primary biochemical defects in both forms of NF is not yet known, but is of great fundamental interest in view of the potential role of these genes in controlling proliferation and differentiation of neural crest cells. Here we discuss different molecular-genetic approaches towards identifying these defective genes. In particular, our studies on tumors associated with BANF have specifically implicated chromosome 22 as the location of the gene defect causing this serious neurological disorder. The identification and characterization of the NF genes, based on their chromosomal localizations, will have profound implications for diagnosis and treatment of these diseases and might yield significant insights into mechanisms controlling development and differentiation of the human nervous system.
UI - 3105404
AU - Carey JC; Baty BJ; Johnson JP; Morrison T; Skolnick M; Kivlin J
TI - The genetic aspects of neurofibromatosis.
SO - Ann N Y Acad Sci 1986;486():45-56
Although the genetic pattern in NF has been definitely established as autosomal dominant, more precise data regarding penetrance, natural history, prevalence, and heterogeneity are needed for the counseling of families. NF is the prototypic disorder for the study of the biologic mechanisms of variable expressivity. The widely cited prevalence figure of Crowe is probably too high; thus the mutation ratio estimation in NF is among the highest in man but close to other common Mendelian disorders. With the existing data on frequency of Lisch nodules and with future prospective date on cafe-au-lait spot development, an age-of-onset penetrance curve for NF could be constructed for genetic counseling purposes. The segmental form of NF is of interest as cases of this presentation may be helpful in studying the hypothesis of human somatic mutation when DNA analysis is available. Guidelines for routine evaluation and ongoing health supervision of individuals with neurofibromatosis need to be developed; multidisciplinary NF clinics and collaborative study groups are appropriate settings for this undertaking. Neurofibromatosis is an important disorder for the study of the psychodynamic processes that families experience in dealing with uncertainty.
UI - 3149475
AU - Gray J; Swaiman KF
TI - Brain tumors in children with neurofibromatosis: computed tomography and magnetic resonance imaging.
SO - Pediatr Neurol 1987 Nov-Dec;3(6):335-41
AD - Division of Pediatric Neurology, University of Minnesota Medical School, Minneapolis 55455.
Comparisons were made between the results of computed tomography and magnetic resonance imaging (MRI) evaluations in 13 patients with neurofibromatosis. In 8 of 9 patients with intracranial tumors and in 2 of 4 patients without intracranial tumors additional findings were demonstrated by MRI.
UI - 6437664
AU - Kao YS; Kao-Shan CS; Knutsen T; Whang-Peng J; Mulvihill JJ
TI - Neurofibromatosis: no chromosomal defect by prophase banding technique.
SO - Cancer Genet Cytogenet 1984 Nov;13(3):281-2
UI - 6239015
AU - Simpson JM
TI - Neurological disorders with autosomal dominant transmission.
SO - J Neurosurg Nurs 1984 Oct;16(5):262-9
Neurofibromatosis, Huntington's disease, and myotonic dystrophy are three hereditary disorders affecting the nervous system. They have in common the basic principles of autosomal dominant inheritance: an affected individual has one parent with the disorder; the disorder affects males and females in approximately equal numbers; and an affected individual has a 50 percent risk of transmitting the disorder to every child. Furthermore, each of the three disorders have additional features that complicate genetic counseling and decisions about reproduction. Neurofibromatosis has an extremely variable expressivity, making the identification of affected individuals difficult and allowing for some reduction in the risk figures; although there is a 50 percent risk of a child inheriting the mutant gene, only one-fourth to one-third of these will experience serious consequences. Huntington's disease has a fairly typical course with degeneration occurring over 10 to 20 years. The frequent late onset of the disorder and the lack of any preclinical test for detecting carriers create problems for those at risk who wish to have children but do not want to pass the disorder to future generations. Both variable expressivity and variable onset are found in myotonic dystrophy. In addition, there is a risk of the severe early onset myotonic dystrophy when the mother is the affected parent. Genetic counseling should be available to patients and families with these three disorders. Nurses who have an understanding of the dynamics of these particular disorders can be empathetic to patients who face personal and family problems caused by the conditions. Alert nursing staff, in casual discussion with patients, may learn of hereditary disorders in a family or may notice symptoms that could lead to diagnosis of one of these disorders. Finally, nurses who are aware of the variations in genetic transmission of these disorders, may be in position to instruct and reinforce genetic counseling that the family has received.
UI - 2491896
AU - Kaneko Y; Maseki N; Sakurai M; Shibuya A; Shinohara T; Fujimoto T; Kanno
TI - H; Nishikawa A Chromosome pattern in juvenile chronic myelogenous leukemia, myelodysplastic syndrome, and acute leukemia associated with neurofibromatosis.
SO - Leukemia 1989 Jan;3(1):36-41
AD - Department of Laboratory Medicine, Saitama Cancer Center, Japan.
We studied chromosomes of BM cells from four neurofibromatosis (NF) patients with leukemia. One patient had a normal diploid karyotype in the chronic phase of juvenile chronic myelogenous leukemia (JCML). When the the leukemia evolved into the accelerated phase, she had cells with 46,XX,-7,+der(7)t(3;7)(q21;p22); the abnormalities resulted in a partial 7p deletion. In another patient with JCML, BM cells in the accelerated phase had 45,XY,-7. The abnormal cells with monosomy 7 disappeared from the BM after chemotherapy but reappeared later in the course. Another patient developed refractory anemia with excess of blasts in transformation (RAEB-T) and had cells with 46,XX,-6,+r(6)(p23?q21?); the abnormalities resulted in partial 6p and 6q deletions. The other patient with ANLL had cells with 45,XX,-7. Our findings and review of data on nine other patients suggest that BM cells of NF patients with JCML in chronic phase have no microscopically detectable chromosome changes and that cells with chromosomal deletion emerge when JCML evolve into the accelerated or blast phase. Thus, deletion of the whole or part of certain chromosomes, such as chromosomes 6, 7, etc., may be an important step towards the evolution of JCML cells or the development of de novo acute leukemias in NF patients.
UI - 7811422
AU - Legius E; Descheemaeker MJ; Fryns JP; Van den Berghe H
TI - Neurofibromatosis type 1.
SO - Genet Couns 1994;5(3):225-41
AD - Center for Human Genetics, University of Leuven, Belgium.
The authors review the present data on the clinical and molecular aspects of neurofibromatosis type 1 (NF1). In the clinical part attention is given to the frequent observation of learning disabilities in NF1 children. In these children visual-spatial integration deficits and an increased incidence of school performance problems are observed. The NF1 gene is located on chromosome 17 (17q11.2), and is highly conserved across species. Up to now only a limited number of mutations in this gene have been characterized, and this shows a general lack of genotype-phenotype correlation. Evidence is given that the NF1 gene acts as a true tumor suppressor gene and that oncogenesis in NF1 is a complex multistep phenomenon with the second hit in the NF1 gene as the initiating event. The importance of specialized multidisciplinary outpatient clinics for neurofibromatosis is emphasized because of the complexity of follow-up and treatment of these patients.
UI - 7696678
AU - Pikus AT
TI - Pediatric audiologic profile in type 1 and type 2 neurofibromatosis.
SO - J Am Acad Audiol 1995 Jan;6(1):54-62
AD - Neuro-Otology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland.
The neurofibromatoses with two subclasses known as NF1 and NF2 are two genetically distinct, autosomal dominantly inherited conditions with significant ramifications in the human auditory system. NF1 is a multisystem progressive disorder that can frequently involve portions of the auditory system in diverse and subtle ways and in which no characteristic audiologic findings can be discerned. NF2 is characterized by the presence of bilateral vestibular schwannomas, sometimes associated with multiple intracranial and spinal tumors. In 43 children with NF1, significant auditory system involvement was found by pure-tone, immittance, and auditory brainstem response (ABR) evaluation. Indications are that audiologists need to contribute to the diagnosis and management in this condition. In 13 children with NF2, handicapping hearing loss was not the primary or usual presenting symptom. However, current findings suggest that ABR and acoustic reflex studies are always indicated in the pediatric NF2 population and are as valid and significant as in adults with NF2.
UI - 7718870
AU - Luna-Fineman S; Shannon KM; Lange BJ
TI - Childhood monosomy 7: epidemiology, biology, and mechanistic implications.
SO - Blood 1995 Apr 15;85(8):1985-99
AD - Department of Pediatrics, University of California, San Francisco 94143-0724, USA.
UI - 7619195
AU - Leao M; da Silva ML
TI - Evidence of central nervous system involvement in Watson syndrome.
SO - Pediatr Neurol 1995 Apr;12(3):252-4
AD - Department of Neurology and Neurosurgery, Hospital de S. Joao, Porto, Portugal.
In 1967, Watson described 3 families with an autosomal dominant condition characterized by pulmonary valvular stenosis, cafe-au-lait sports, and short stature. Presumed hamartomatous lesions have been observed in neurofibromatosis type I, but they were not reported to date in Watson syndrome. We report another family with Watson syndrome, in which 1 patient manifested increased intensity T2-weighted lesions on magnetic resonance imaging similar to those occurring in neurofibromatosis type I and possibly hamartomas. This finding demonstrates the overlap between neurofibromatosis type I and Watson syndrome and supports the hypothesis that those conditions are allelic or, less likely, that the gene that determines the Watson phenotype is very closely linked to the neurofibromatosis type I locus.
UI - 7479890
AU - Knudson A
TI - Asbestos and mesothelioma: genetic lessons from a tragedy.
SO - Proc Natl Acad Sci U S A 1995 Nov 21;92(24):10819-20
AD - Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
UI - 8559307
AU - Ng HK; Lau KM; Tse JY; Lo KW; Wong JH; Poon WS; Huang DP
TI - Combined molecular genetic studies of chromosome 22q and the neurofibromatosis type 2 gene in central nervous system tumors.
SO - Neurosurgery 1995 Oct;37(4):764-73
AD - Department of Anatomical & Cellular Pathology, Chinese University of Hong Kong, Hong Kong.
Monosomy of chromosome 22 or deletions of 22q have been described in meningiomas and astrocytic tumors, the incidence of which is increased in Type 2 neurofibromatosis. Recently, the gene for neurofibromatosis Type 2 (NF2) has been identified at Chromosome 22q12, and a tumor suppression role has been suggested. Because there have been only a few studies of the NF2 gene on central nervous system tumors other than vestibular schwannomas, we investigated the potential role of NF2 as a tumor suppressor gene in a group of sporadic meningiomas and astrocytomas. Forty-four tumors (26 meningiomas and 18 astrocytic tumors of different grades) were screened for NF2 mutations for the