A Common Set of at Least 11 Functional Genes Is Lost in the Majority of NF1 Patients with Gross Deletions

Jenne, Dieter E.; Tinschert, Sigrid; Stegmann, Elisabeth; Reimann, Heike; Nürnberg, Peter; Horn, Denise; Naumann, Ilka; Buske, Annegret; Thiel, Gundula

doi:10.1006/geno.2000.6179

Cited by 41 publications

(38 citation statements)

References 15 publications

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“…The same BAC probes were previously found to delimit the deleted segment in the majority of NF1 patients with microdeletions. 16 Similar findings on the breakpoint locations in NF1 microdeletions were recently published by Dorschner et al 17 In all fibroblasts from the patient we observed two signals with the BACs R-271K11 and R-640N20, but we obtained only one signal with the BACs 2309P3 and 307A16 in about 15% of fibroblasts derived from skin biopsies of the affected body region similar to the results with intragenic probes. These findings clearly establish the clonal origin of segmental NF1 manifestations in our patient and excludes the loss of variable portions of the long arm of chromosome 17 in affected fibroblasts.…”

Section: Resultssupporting

confidence: 91%

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Segmental neurofibromatosis is caused by somatic mutation of the neurofibromatosis type 1 (NF1) gene

et al. 2000

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Segmental neurofibromatosis (NF) is generally thought to result from a postzygotic NF1 (neurofibromatosis type 1) gene mutation. However, this has not yet been demonstrated at the molecular level. Using fluorescence in situ hybridisation (FISH) we identified an NF1 microdeletion in a patient with segmental NF in whom café-au-lait spots and freckles are limited to a single body region. The mutant allele was present in a mosaic pattern in cultured fibroblasts from a café-au-lait spot lesion, but was absent in fibroblasts from normal skin as well as in peripheral blood leukocytes. These findings prove the hypothesis that the molecular basis of segmental cutaneous NF is a mutation in the NF1 gene and that the regional distribution of manifestations reflects different cell clones, commensurate with the concept of somatic mosaicism.

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Section: Resultssupporting

confidence: 91%

“…The partially overlapping BACs R-271K11 and 2309P3 flank the proximal breakpoint region, whereas the contiguous BACs 307A16 and R-640N20 surround the distal breakpoints in five out of seven patients with microdeletions. 16 …”

Section: Cosmid and Bac Probesmentioning

confidence: 99%

Segmental neurofibromatosis is caused by somatic mutation of the neurofibromatosis type 1 (NF1) gene

et al. 2000

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“…The present study has identified at least 10 genes whose mutations increased GCR rates and the human homologs of which might be found in GCR-prone human cancers. Indeed, there have been many recent reports (46)(47)(48)(49)(50)(51) supporting the concept that genes identified in our screen have importance in cancer development. Abnormal expression of human TSA1 in many different cancers and severe hemolytic anemia and several malignant cancers in mice lacking murine homolog of TSA1 gene, Prdx1, were observed.…”

Section: Discussionmentioning

confidence: 68%

Mutator genes for suppression of gross chromosomal rearrangements identified by a genome-wide screening in Saccharomyces cerevisiae

Smith

Hwang

Banerjee

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

135

151

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Different types of gross chromosomal rearrangements (GCRs), including translocations, interstitial deletions, terminal deletions with de novo telomere additions, and chromosome fusions, are observed in many cancers. Multiple pathways, such as S-phase checkpoints, DNA replication, recombination, chromatin remodeling, and telomere maintenance that suppress GCRs have been identified. To experimentally expand our knowledge of other pathway(s) that suppress GCRs, we developed a generally applicable genome-wide screening method. In this screen, we identified 10 genes (ALO1, CDC50, CSM2, ELG1, ESC1, MMS4, RAD5, RAD18, TSA1, and UFO1) that encode proteins functioning in the suppression of GCRs. Moreover, the breakpoint junctions of GCRs from these GCR mutator mutants were determined with modified breakpoint-mapping methods. We also identified nine genes (AKR1, BFR1, HTZ1, IES6, NPL6, RPL13B, RPL27A, RPL35A, and SHU2) whose mutations generated growth defects with the pif1⌬ mutation. In addition, we found that some of these mutations changed the telomere size.

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“…In two of them (COS and PFA), the deletion breakpoints were determined by deletion junction-specific PCRs and found to be located in the 4 kb hotspot interval of the type I deletion. 24,25 Four patients with optic pathway glioma were not included in the present study since optic glioma is a rare cause of overgrowth and precocious puberty. 26 -30 Precocious puberty was noticed in patient COS.…”

Section: Methodsmentioning

confidence: 99%

Childhood overgrowth in patients with common NF1 microdeletions

et al. 2005

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While growth retardation and short stature are well-known features of patients with classical neurofibromatosis type 1 (NF1), we found advanced height growth and accelerated carpal bone age in patients with an NF1 microdeletion. Our analysis is based on growth data of 21 patients with common 1.4/1.2 Mb microdeletions, including three patients with a Weaver-like appearance. Overgrowth was most evident in preschool children (2-6 years, n ¼ 10, P ¼ 0.02). We conclude that childhood overgrowth is part of the phenotypic spectrum in patients with the common 1.4/1.2 Mb NF1 microdeletions and assume that the chromosomal region comprised by the microdeletions contains a gene whose haploinsufficiency causes overgrowth.

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A Common Set of at Least 11 Functional Genes Is Lost in the Majority of NF1 Patients with Gross Deletions

Cited by 41 publications

References 15 publications

Segmental neurofibromatosis is caused by somatic mutation of the neurofibromatosis type 1 (NF1) gene

Segmental neurofibromatosis is caused by somatic mutation of the neurofibromatosis type 1 (NF1) gene

Mutator genes for suppression of gross chromosomal rearrangements identified by a genome-wide screening in Saccharomyces cerevisiae

Childhood overgrowth in patients with common NF1 microdeletions

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