Showing papers by "Guy A. Rouleau published in 1987"
TL;DR: The genetic localization of the primary BANF defect strongly supports the concept that the disease locus encodes a 'tumour suppressor' gene, and should provide insights into the pathogenesis of acoustic neuromas and other nervous system tumours.
Abstract: Bilateral acoustic neurofibromatosis (BANF) is a severe autosomal dominant disorder involving development of multiple tumours of the nervous system including meningiomas, gliomas, neurofibromas and particularly bilateral acoustic neuromas. We have used genetic linkage analysis with DNA markers to establish that the defective gene causing BANF is on chromosome 22, and is therefore distinct from the gene for the von Recklinghausen form of neurofibromatosis, which maps to chromosome 17. Linked DNA markers will be particularly valuable in BANF, facilitating early detection of tumours and thereby permitting more effective surgical intervention. In view of the reported loss of genes on chromosome 22 in meningiomas and acoustic neuromas, the genetic localization of the primary BANF defect strongly supports the concept that the disease locus encodes a 'tumour suppressor' gene. Isolation of this gene should provide insights into the pathogenesis of acoustic neuromas and other nervous system tumours, as well as into the control of proliferation and differentiation of neural crest cells.
421 citations
TL;DR: The VRNF gene is genetically linked to the locus encoding nerve growth factor receptor, located on the long arm of chromosome 17 in the region 17q12----17q22, and crossovers with the VRNF locus suggest that a mutation in the nerve growthFactor receptor gene itself is unlikely to be the fundamental defect responsible for the VR NF phenotype.
343 citations
TL;DR: Specific loss of alleles from chromosome 22 was detected with polymorphic DNA markers in two acoustic neuromas, two neurofibromas, and one meningioma from BANF patients, indicating a common pathogenetic mechanism for all three tumor types.
Abstract: Bilateral acoustic neurofibromatosis (BANF) is a genetic defect associated with multiple tumors of neural crest origin. Specific loss of alleles from chromosome 22 was detected with polymorphic DNA markers in two acoustic neuromas, two neurofibromas, and one meningioma from BANF patients. This indicates a common pathogenetic mechanism for all three tumor types. The two neurofibromas were among three taken from the same patient, and both showed loss of identical alleles demonstrating that the same chromosome suffered deletion in both tumors. The third neurofibroma from this patient showed no detectable loss of heterozygosity, which suggests the possibility of a more subtle mutational event that affects chromosome 22. In the two acoustic neuromas, only a portion of chromosome 22 was deleted, narrowing the possible chromosomal location of the gene that causes BANF to the region distal to the D22S9 locus in band 22q11. The identification of progressively smaller deletions on chromosome 22 in these tumor types may well provide a means to clone and characterize the defect.
234 citations
TL;DR: There was a significantly more marked atrophy of all fiber types in the DEX‐DEN plantares at 7 and 13 days than in either DEX or DEN muscles, which may be due to a severe preferential inhibition of its synthesis coupled with an accelerated catabolism.
Abstract: The combined effects of dexamethasone treatment (1 mg/Kg/day) plus denervation (DEX-DEN), were studied at 7, 13, and 28 days by microscopic, biochemical, and physiological techniques in plantaris and soleus muscles of adult rats. The results were compared with corresponding dexamethasone-treated (DEX) and denervated (DEN) muscles and appropriate controls. There was a significantly more marked atrophy of all fiber types in the DEX-DEN plantares at 7 and 13 days than in either DEX or DEN muscles. The degree of atrophy was greatest in type 2B fibers in DEX-DEN plantares. Electron microscopy revealed a severe preferential depletion of thick myofilaments in DEX-DEN plantares and solei but not in DEX or DEN muscles. The thick myofilament depletion in DEX-DEN muscles occurred in addition to a severe overall reduction of myofibrillar caliber. Gel electrophoresis showed a marked preferential decrease of myosin heavy chain in DEX-DEN plantares and solei, but not in either DEX or DEN muscles. Myosin light chains were also markedly reduced in DEX-DEN plantares and solei. In vitro physiological studies showed a marked reduction of the denervation-induced twitch potentiation in DEX-DEN solei. Maximal tetanic tension (20 Hz stimulation) per gram weight of muscle as well as the twitch-tetanus ratio was significantly reduced only in DEX-DEN solei in relation to controls. Myosin depletion in DEX-DEN muscles may be due to a severe preferential inhibition of its synthesis coupled with an accelerated catabolism.
122 citations
TL;DR: Linkage analysis with the human oncogene homolog erbA1, which maps to this region, suggests that this cancer-related gene is not the primary cause of NF1, and a preliminary multipoint linkage analysis suggests that the NF1 gene is located on the long arm of chroomsome 17.
24 citations
TL;DR: DNA linkage analysis in 11 families with Von Recklinghausen neurofibromatosis in order to search for the chromosomal localisation of the defective gene causing this serious neurological disorder excludes close linkage between any of the polymorphic DNA markers used.
Abstract: We have used DNA linkage analysis in 11 families with Von Recklinghausen neurofibromatosis (VRNF) in order to search for the chromosomal localisation of the defective gene causing this serious neurological disorder. Three groups of polymorphic DNA markers were used: (1) markers for chromosome 22, because of possible allelic genetic heterogeneity between VRNF and bilateral acoustic neurofibromatosis; (2) markers near the centromere of chromosome 4, since there was preliminary evidence for linkage between the VRNF gene and Gc; and (3) oncogenes and growth factors as possible candidate genes for VRNF. Our data exclude close linkage between any of these markers and the gene for VRNF.
12 citations
TL;DR: Different molecular-genetic approaches towards identifying 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.
Abstract: 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
5 citations