scholarly journals Identification of a germline CSPG4 variation in a family with neurofibromatosis type 1-like phenotype

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Zhuanli Bai ◽  
Yiping Qu ◽  
Lin Shi ◽  
Xinju Li ◽  
Zhen Yang ◽  
...  
Keyword(s):  
Neurofibromatosis Type 1 ◽  
De Novo ◽  
Neurofibromatosis Type ◽  
Multisystem Disorder ◽  
Functional Studies ◽  
Whole Exome ◽  
Germline Variation ◽  
Increased Susceptibility

AbstractNeurofibromatosis type 1 (NF1), an autosomal dominant and multisystem disorder, is generally considered to be caused by NF1 inactivation. However, there are also numerous studies showing that Neurofibromatosis type 1-like phenotype can be caused by the abnormalities in the other genes. Through targeted parallel sequencing, whole-exome sequencing, de novo genomic sequencing, and RNA isoform sequencing, we identified a germline V2097M variation in CSPG4 gene probably increased susceptibility to a NF1-like phenotype family. Besides, a series of in vitro functional studies revealed that this variant promoted cell proliferation by activating the MAPK/ERK signaling pathway via hindering ectodomain cleavage of CSPG4. Our data demonstrate that a germline variation in the CSPG4 gene might be a high risk to cause NF1-like phenotype. To our knowledge, this is the first report of mutations in the CSPG4 gene in human diseases.

scholarly journals Establishing the diagnosis neurofibromatosis type 1: A rare case

2019 ◽  
Author(s):  
Dyatiara Devy ◽  
D. Damayanti
Keyword(s):  
Neurofibromatosis Type 1 ◽  
De Novo ◽  
Malignant Tumors ◽  
Neurofibromatosis Type ◽  
The Body ◽  
Multisystem Disorder ◽  
Wide Range ◽  
Multidisciplinary Clinic ◽  
History Of

Neurofibromatosis type 1 (NF1) or Von Recklinghausen's disease is a dominantly inherited genetic, multisystem disorder. Individuals with neurofibromatosis type 1 are prone to develop benign and malignant tumors of the CNS and peripheral nervous system, in addition to malignant diseases affecting other parts of the body. About 50% of individuals with neurofibromatosis type 1 have no family history of the disease and the disease is due to de novo (spontaneous) mutations. Early diagnosis is challenging because of its extremely variable characteristics. Some individuals may be mildly affected showing minimal signs, whereas others are severely afflicted. Individuals with NF-1 are best cared for within a multidisciplinary clinic, which has access to a wide range of subspecialists. The dermatologist has a role not only in the diagnosis of NF1 and differentiating it from other similar disorders, but also in the recognition of rare associated skin manifestations.

scholarly journals Case report of ascending colon cancer and multiple jejunal GISTs in a patient with neurofibromatosis type 1 (NF1)

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Liang Shang ◽  
Zhen Fang ◽  
Jin Liu ◽  
Fengying Du ◽  
Haiyan Jing ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Ascending Colon ◽  
Malignant Tumours ◽  
Whole Exome ◽  
Ascending Colon Cancer

Abstract Background NF1(Neurofibromatosis type 1) is an autosomal dominant genetic disorder. Patients with NF1 have an increased risk of developing benign or malignant tumours, such as gastrointestinal stromal tumours (GISTs). However, the coexistence of NF1, GIST and colon cancer is very rare, and few cases have been reported in the literature. Case presentation We admitted a case of a 64-year-old man with type 1 neurofibromatosis, GISTs, and ascending colon cancer. This case was characterized by café-au-lait macules, discrete cutaneous neurofibromas, nodular neurofibromas, multiple jejunal tumours, and ascending colon cancer. Laparoscopic exploration revealed ascending colon cancer and multiple jejunal tumours. Laparoscopic right hemicolectomy and local excision of the jejunal tumours were performed successfully. The pathological results confirmed moderate differentiated adenocarcinoma of the ascending colon with multiple jejunal GISTs (low risk, very low risk). Moreover, the immunohistochemistry results of multiple jejunal GISTs suggest that NF1 is positive. Whole-exome sequencing (WES) of colon cancer revealed mutations in more than 20 genes, including KRAS, PIK3CA, APC, SMAD4, etc. The results of whole-exome sequencing (WES) of jejunal GISTs revealed an NF1 mutation and no KIT or PDGFR gene mutation. Conclusion We report a rare case of simultaneous NF1, GIST and colon adenocarcinoma. For patients with NF1, benign and/or malignant tumours are often combined. Therefore, these patients should undergo regular physical examinations so that early detection and early treatment can be achieved.

Mutations of the NF1 Gene in Children With Juvenile Myelomonocytic Leukemia Without Clinical Evidence of Neurofibromatosis, Type 1

Blood ◽  
1998 ◽  
Vol 92 (1) ◽  
pp. 267-272 ◽  
Author(s):  
Lucy E. Side ◽  
Peter D. Emanuel ◽  
Brigit Taylor ◽  
Janet Franklin ◽  
Patricia Thompson ◽  
...  
Keyword(s):  
Clinical Diagnosis ◽  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Juvenile Myelomonocytic Leukemia ◽  
Translation System ◽  
Polymorphism Analysis ◽  
Single Stranded Conformational Polymorphism ◽  
Myelomonocytic Leukemia

Juvenile myelomonocytic leukemia (JMML) is a pediatric myelodysplastic syndrome that is associated with neurofibromatosis, type 1 (NF1). The NF1 tumor suppressor gene encodes neurofibromin, which regulates the growth of immature myeloid cells by accelerating guanosine triphosphate hydrolysis on Ras proteins. The purpose of this study was to determine if the NF1gene was involved in the pathogenesis of JMML in children without a clinical diagnosis of NF1. An in vitro transcription and translation system was used to screen JMML marrows from 20 children for NF1mutations that resulted in a truncated protein. Single-stranded conformational polymorphism analysis was used to detect RASpoint mutations in these samples. We confirmed mutations of NF1in three leukemias, one of which also showed loss of the normalNF1 allele. An NF1 mutation was detected in normal tissue from the only patient tested and this suggests that JMML may be the presenting feature of NF1 in some children. Activating RASmutations were found in four patients; as expected, none of these samples harbored NF1 mutations. Because 10% to 14% of children with JMML have a clinical diagnosis of NF1, these data are consistent with the existence of NF1 mutations in approximately 30% of JMML cases.

Serum mitogenic activity on in vitro glial cells in Neurofibromatosis type 1

1998 ◽  
Vol 793 (1-2) ◽  
pp. 21-28 ◽  
Author(s):  
Brunella Caronti ◽  
Francesca Romana Buttarelli ◽  
Sandra Giustini ◽  
Caterina Calderaro ◽  
Luigi Calandriello ◽  
...  
Keyword(s):  
Glial Cells ◽  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Mitogenic Activity

Neurofibromin-deficient fibroblasts fail to form perineurium in vitro

Development ◽  
1995 ◽  
Vol 121 (11) ◽  
pp. 3583-3592
Author(s):  
T. Rosenbaum ◽  
Y.L. Boissy ◽  
K. Kombrinck ◽  
C.I. Brannan ◽  
N.A. Jenkins ◽  
...  
Keyword(s):  
Schwann Cells ◽  
Neurofibromatosis Type 1 ◽  
Fibroblast Cell ◽  
Neurofibromatosis Type ◽  
Type I ◽  
Nerve Sheath Tumors ◽  
Cell Strains ◽  
Perineurial Cells

To identify cell type(s) that might contribute to nerve sheath tumors (neurofibromas) in patients with neurofibromatosis type 1, we generated cell cultures containing neurons. Schwann cells and fibroblasts from transgenic mouse embryos in which the type 1 neurofibromatosis gene was disrupted by homologous recombination (Brannan et al. (1994) Genes Development, 8,1019-1029). Normal fascicle formation by perineurial cells failed to occur in the absence of neurofibromin. Fascicles were reduced in number and showed abnormal morphology when normal neurons and Schwann cells were cultured up to 37 days with fibroblasts lacking neurofibromin. Proliferation was increased in a majority of fibroblast cell strains analyzed from embryos lacking neurofibromin. These observations suggest that mutations in the neurofibromatosis type I gene affect fibroblast behavior that might contribute to neurofibroma formation in patients with neurofibromatosis type 1.

scholarly journals Single-sperm analysis for haplotype construction of de-novo paternal mutations: application to PGD for neurofibromatosis type 1

2006 ◽  
Vol 21 (8) ◽  
pp. 2047-2051 ◽  
Author(s):  
G. Altarescu ◽  
B. Brooks ◽  
Y. Kaplan ◽  
T. Eldar-Geva ◽  
E.J. Margalioth ◽  
...  
Keyword(s):  
Neurofibromatosis Type 1 ◽  
De Novo ◽  
Neurofibromatosis Type ◽  
Sperm Analysis

Three different pathological lesions in the NF1 gene originating de novo in a family with neurofibromatosis type 1

2003 ◽  
Vol 112 (1) ◽  
pp. 12-17 ◽  
Author(s):  
Meena Upadhyaya ◽  
Elisa Majounie ◽  
Peter Thompson ◽  
Song Han ◽  
Claudia Consoli ◽  
...  
Keyword(s):  
Neurofibromatosis Type 1 ◽  
De Novo ◽  
Neurofibromatosis Type ◽  
Pathological Lesions ◽  
Nf1 Gene

scholarly journals TATA-Binding Protein (TBP)-Like Factor (TLF) Is a Functional Regulator of Transcription: Reciprocal Regulation of the Neurofibromatosis Type 1 and c-fos Genes by TLF/TRF2 and TBP

2005 ◽  
Vol 25 (7) ◽  
pp. 2632-2643 ◽  
Author(s):  
Jayhong A. Chong ◽  
Magdalene M. Moran ◽  
Martin Teichmann ◽  
J. Stefan Kaczmarek ◽  
Robert Roeder ◽  
...  
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Binding Protein ◽  
Neurofibromatosis Type ◽  
Tata Binding Protein ◽  
Related Factor ◽  
Reciprocal Regulation ◽  
In Cells

ABSTRACT The lack of direct targets for TATA-binding protein (TBP)-like factors (TLFs) confounds the understanding of their role in gene expression. Here we report that human TLF (also called TBP-related factor 2 [TRF2]) activates a number of different genes, including the neurofibromatosis type 1 (NF1) gene. The overexpression of TLF increases the amount of NF1 mRNA in cells. In vivo, TLF binds to and upregulates transcription from a fragment of the NF1 promoter. In vitro, purified TLF-TFIIA binds directly to the same NF1 promoter fragment that is required for TLF responsiveness in cells. Furthermore, targeted deletion of TLF in mice reduces NF1 levels. In contrast, TLF inhibits transcription driven by a fragment from the TATA-containing c-fos promoter by sequestering TFIIA. TBP affects the NF1 and c-fos promoters in a manner reciprocal to that of TLF, stimulating the c-fos promoter and inhibiting NF1 transcription. We conclude that TLF is a functional regulator of transcription with targets distinct from those of TBP.

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