1/10. Somatic mosaicism of a greater than 1.7-Mb deletion of genomic dna involving the entire NF1 gene as verified by FISH: further evidence for a contiguous gene syndrome in 17q11.2.We report on a third case with neurofibromatosis type 1 (NF1) due to mosaicism for a gross deletion in 17q11.2 covering the entire NF1 gene. The deletion was suspected in Giemsa banded chromosomes and was confirmed by fluorescence in situ hybridization using the cosmids CO919 from the 5' region, GO2121 from the central, H10410 from the 3' region of the NF1 gene, and the 1.7-Mb YAC 947G11 spanning the entire 350-kb genomic dna of the NF1 gene. The deletion was present in 33% of peripheral blood lymphocytes and 58% of fibroblasts. The clinical manifestations in this 6-year-old male patient were especially severe and extended beyond the typical features of NF1. The patient also displayed facial anomalies, severe and early-onset psychomotor retardation, seizures, spasticity, and microcephaly. These features differ from other large-deletion NF1 patients, even nonmosaic cases. The complex phenotype could be explained by the involvement of coding sequences flanking the NF1 gene, thus supporting the existence of a contiguous gene syndrome in 17q11.2.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/10. Pigmented (melanotic) neurofibroma. Report of an unusual case with immunohistochemical, ultrastructural and cytogenetic analyses.In the spectrum of neurofibromas, pigmented tumors are rare variants usually showing only faint, macroscopically obvious pigmentation. We report a case of a huge pigmented neurofibroma with extended, macroscopically striking pigmentation in a patient with stigmata of neurofibromatosis. The immunohistochemical and ultrastructural findings support a melanotic line of differentiation besides schwann cell differentiation and indicate a phenotypic neoplastic spectrum between tumorous schwann cells and melanocytes. Using comparative genomic hybridization, striking chromosomal aberrations were not detected. High level amplifications of the known chromosomal regions, including genes of major enzymes responsible for melanin synthesis, appear to be unlikely. However, smaller chromosomal defects might have been overlooked by the limited resolution of this screening method. Therefore, other mechanisms up-regulating melanogenesis, such as mutations in regulatory genes, have to be considered.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
3/10. Vasculopathy in two cases of NF1-related congenital pseudarthrosis.Neurofibromatosis type 1 (NF1) is a common dominantly inherited disease. More than half of NF1 patients suffer from skeletal manifestations, of which congenital pseudarthrosis of tibia (CPT) is one of the most incapacitating lesions. Two NF1 patients with CPT were operated, and the resected tissues were analyzed using immunohistochemistry and/or in situ hybridization for NF1 protein and mRNA, p-p44/42 MAPK, and S100 protein. Both patients displayed thick-walled arteries and veins with a small lumen within the fibrotic tissue in the vicinity of pseudarthrosis. endothelial cells were highly positive for p-p44/42 MAPK. A subpopulation of cells surrounding the blood vessels was S100 protein-positive. However, the exact identity of the S100-positive cells remains to be elucidated. Neurofibromin mRNA and protein labeling was detected in both cell types. In conclusion, decreased NF1 function as a RAS-GAP in the endothelium may contribute to vascular thickening in CPT.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
4/10. chromosomes 17 and 22 involved in marker formation in neurofibrosarcoma in von Recklinghausen disease. A cytogenetic and in situ hybridization study.We describe the cytogenetic findings in a recurrent neurofibrosarcoma in a patient with nonfamilial von Recklinghausen disease. The composite karyotype was: 40,Y,-X, dic r(X;20)(:Xp22.2 q26::20p13 q13:), -1, der(1)t(1;3) (p21;p24),-3,-4,-5, der(5) t(5;?)(q31;?),-9,-9, der(9)t(3;9)(q21 or q13;p24 or p22), -11, der(11)t(11;?)(q22.2;?), -17, der(17)t(17; 22;?)(q21;q13.1;?), -20, -21, -22, -22, der(22)t(17; 22;?)(q21;q13.1;?),t(2;10)(q37;q22). The derivative chromosomes were demonstrated at the 500 band level. chromosomes 17 and 22 were shown to be involved in an unbalanced three-way translocation: t(17;22;?)(q21;q13.1;?). This event was confirmed by in situ hybridization, using two probes mapped to chromosome 17. Hill H is a probe derived from the novel oncogene TRE and is located at 17q12-22. The second probe, derived from the granulocyte colony-stimulating factor (G-CSF), is located at 17q11-q21. The rearrangement between chromosomes 17 and 22 showed breakpoints similar or close to the gene loci for neurofibromatosis 1 (NF-1) and NF-2. Based on our observations we recommend that genetic studies on NF-1 tumors include both gene sites (NF-1 and NF-2) rather than focus on one gene locus.- - - - - - - - - - ranking = 5keywords = hybridization (Clic here for more details about this article) |
5/10. Familial occurrence of neuroblastoma, von Recklinghausen's neurofibromatosis, Hirschsprung's agangliosis and jaw-winking syndrome.A family is reported with ganglioneuromas in the mother and neuroblastomas in her two daughters co-existing with cases of von Recklinghausen's neurofibromatosis, Hirschsprung's agangliosis, and the jaw-winking syndrome in other family members. There were no detectable constitutional chromosomal defects in the family even when high resolution techniques were applied. Similarly, dna-hybridization analysis did not reveal gross molecular rearrangements in the vicinity of the proto-oncogenes N-myc-, c-myc, neu, and N-ras. However, the aggregation of several rare, autosomal dominant diseases affecting tissue derived from the neural crest not only suggest a link between te pathogenesis of these disease, but also makes it highly likely that a single mutation segregating within the family is responsible for this association.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
6/10. Neurofibromatosis in a man with a ring 22: in situ hybridization studies.in situ hybridization with a c-sis probe was performed on peripheral lymphocytes of a man with neurofibromatosis and a ring 22 chromosome. Hybridization was observed on both the normal #22 and the ring 22, indicating that the patient is not constitutionally hemizygous for c-sis. The implications of a ring 22 constitution and the neurofibromatosis phenotype are discussed.- - - - - - - - - - ranking = 5keywords = hybridization (Clic here for more details about this article) |
7/10. Characterization of a de novo 48,XX, r(X), r(17) by in situ hybridization in a patient with neurofibromatosis (NF1).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.- - - - - - - - - - ranking = 5keywords = hybridization (Clic here for more details about this article) |
8/10. Characterization of a cytogenetic 17q11.2 deletion in an NF1 patient with a contiguous gene syndrome.We report on a rare patient screened as a putative carrier of a contiguous gene syndrome on the basis of a complex phenotype characterized by sporadic neurofibromatosis type 1 (NF1), dysmorphism, mental retardation and severe skeletal anomalies. A cytogenetically visible 17q11.2 deletion was detected in the patient's karyotype by high-resolution banding and confirmed by fluorescence in situ hybridization with yeast artificial chromosomes targeting the NF1 region. Analysis of the segregation from parents to proband of 13 polymorphic dna markers, either contiguous or contained within the NF1 gene, showed that the patient is hemizygous at sites within the NF1 gene-the AAAT-Alu repeat in the 5' region of intron 27b, the CA/GT microsatellite in the 3' region of intron 27b, and the CA/GT microsatellite in intron 38- and at the extragenic D17S798 locus, distal to the 3' end of NF1. The patient may be an important resource in the identification of genes downstream of NF1 that may contribute to some of his extra-NF1 clinical signs.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
9/10. The second case of a t(17;22) in a family with neurofibromatosis type 1: sequence analysis of the breakpoint regions.A reciprocal t(17;22)(q11.2;q11.2) was found in a female patient with neurofibromatosis type 1 (NF1) and in her affected daughter. sequence analysis of cloned junction fragments traversing the breakpoints allowed the identification of the structures involved in the rearrangement. Aberrant bands in Southern hybridizations of restriction enzyme-digested dna of the patient pointed to the disruption of the NF1 gene in intron 31. Semispecific polymerase chain reaction analysis of the genomic dna of the patient with the specific primer anchored at NF1 exon 31 was used to obtain the breakpoint-spanning fragment of the derivative chromosome 17. The intron 31 sequence turned out to be interrupted within a large irregular (AT) repeat. The chromosome 22-derived sequence of the der(17) junction fragment allowed us to identify cosmids of the corresponding region from a chromosome 22 specific cosmid library. With the support of the breakpoint-spanning cosmids, the chromosome 22 region upstream of the fragment carried by the der(17) was characterized. Primers deduced from the sequence of this upstream region were used in combination with a primer in NF1 intron 31 distal to the breakpoint on chromosome 17 to amplify the der(22) junction fragment. The structure of the junction sequences suggested that the translocation had arisen by unequal homologous recombination between (AT)-rich repeats on chromosome 22 and on chromosome 17 in intron 31 of the NF1 gene. However, our data support the assumption of additional rearrangements prior to, or in the course of, the recombination event, leading to a loss of the sequences between the involved (AT) repeats on chromosome 22. In the direct vicinity of these (AT) repeats, two members of a previously undescribed low-copy repetitive sequence have been found, copies of which are also present on human chromosome 13.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
10/10. Deletion of the entire NF1 gene causing distinct manifestations in a family.We identified a father and son with neurofibromatosis type 1 (NF1) due to a deletion of the entire NF1 gene detected by fluorescence in situ hybridization (FISH). As is the case for others reported to have such large deletions, father and son had severe NF1, including a large number of cutaneous neurofibromas, facial anomalies, large hands, feet, and head, and developmental impairment. They were discordant in that seizures and plexiform neurofibromas occurred only in the propositus. Large NF1 deletions can be compatible with familial transmission and appear to be associated with a distinct phenotype.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
| | Next -> |