Clinical Manifestations and Management of Neurofibromatosis Type 1

Tonsgard, James H.

doi:10.1016/j.spen.2006.01.005

Cited by 199 publications

(205 citation statements)

References 24 publications

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“…The percentage of major clinical phenotypes is in accordance to previous reports (Tonsgard 2006; Jett and Friedman 2010). When patients under 12 years of age were excluded, the incidence of neurofibromas and LNs decreased (Huson 2008).…”

Section: Resultssupporting

confidence: 92%

126 novel mutations in Italian patients with neurofibromatosis type 1

Bianchessi¹,

Morosini²,

Saletti³

et al. 2015

Molec Gen & Gen Med

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Genetic analysis of Neurofibromatosis type 1 (NF1) may facilitate the identification of patients in early phases of the disease. Here, we present an overview of our diagnostic research spanning the last 11 years, with a focus on the description of 225 NF1 mutations, 126 of which are novel, found in a series of 607 patients (513 unrelated) in Italy. Between 2003 and 2013, 443 unrelated patients were profiled by denaturing high pressure liquid chromatography (DHPLC) analysis of 60 amplicons derived from genomic NF1 DNA and subsequent sequencing of heterozygotic PCR products. In addition, a subset of patients was studied by multiplex ligation‐dependent probe amplification (MLPA) to identify any duplications, large deletions or microdeletions present at the locus. Over the last year, 70 unrelated patients were investigated by MLPA and sequencing of 22 amplicons spanning the entire NF1 cDNA. Mutations were found in 70% of the 293 patients studied by DHPLC, thereby fulfilling the NIH criterion for the clinical diagnosis of NF1 (detection rate: 70%); furthermore, 87% of the patients studied by RNA sequencing were genetically characterized. Mutations were also found in 36 of the 159 patients not fulfilling the NIH clinical criteria. We confirmed a higher incidence of intellectual disability in patients harboring microdeletion type 1 and observed a correlation between a mild phenotype and the small deletion c.2970_2972delAAT or the missense alteration in amino acid residue 1809 (p.Arg1809Cys). These data support the use of RNA‐based methods for genetic analysis and provide novel information for improving the management of symptoms in oligosymptomatic patients.

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Section: Resultssupporting

confidence: 92%

126 novel mutations in Italian patients with neurofibromatosis type 1

Bianchessi¹,

Morosini²,

Saletti³

et al. 2015

Molec Gen & Gen Med

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show abstract

“…Among these patients, 5 of 18 (27.8%) developed mental subnormality. The percentage of NF1 patients with mental subnormality, including poor school performance and attention deficit hyperactivity disorder, was as high as 60% in previous studies (89), while in a study focusing on a Taiwanese cohort, the total was less than 5% (3 of 68). The evidence provided in this report suggests that the learning disability in patients with an NF1 mutation in the LRD region is relatively common.…”

Section: Figurementioning

confidence: 75%

Valosin-containing protein and neurofibromin interact to regulate dendritic spine density

Wang¹,

Shih²,

Chen³

et al. 2011

J. Clin. Invest.

104

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Inclusion body myopathy with Paget disease of bone and frontotemporal dementia (IBMPFD) is an autosomal dominant disorder characterized by progressive myopathy that is often accompanied by bone weakening and/or frontotemporal dementia. Although it is known to be caused by mutations in the gene encoding valosin-containing protein (VCP), the underlying disease mechanism remains elusive. Like IBMPFD, neurofibromatosis type 1 (NF1) is an autosomal dominant disorder. Neurofibromin, the protein encoded by the NF1 gene, has been shown to regulate synaptogenesis. Here, we show that neurofibromin and VCP interact and work together to control the density of dendritic spines. Certain mutations identified in IBMPFD and NF1 patients reduced the interaction between VCP and neurofibromin and impaired spinogenesis. The functions of neurofibromin and VCP in spinogenesis were shown to correlate with the learning disability and dementia phenotypes seen in patients with IBMPFD. Consistent with the previous finding that treatment with a statin rescues behavioral defects in Nf1 +/-mice and providing further support for our hypothesis that there is crosstalk between neurofibromin and VCP, statin exposure neutralized the effect of VCP knockdown on spinogenesis in cultured hippocampal neurons. The data presented here demonstrate that there is a link between IBMPFD and NF1 and indicate a role for VCP in synapse formation.

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“…In the first decade of life can arise freckling, optic gliomas and severe scoliosis. Instead, cutaneous neurofibromas and iris Lisch nodules are frequently apparent during the second decade [10].…”

Section: Clinical Features and Diagnosismentioning

confidence: 99%

The Neurofibromatosis type 1:A dominantly inherited tumors-predisposing disorder

et al. 2009

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AbstractNeurofibromatosis type I (NF1) is a hereditary multisystem disease involving the skin and nervous system. It is the most common form of autosomal dominant phakomatoses with 100% penetrance but wide phenotypic variability. The NF1 gene is located on chromosome 17q11.2 and encodes for a tumour suppressor protein. Because affected individuals have an increased risk of tumor formation, this disorder is classified as inherited cancer syndrome. The risk of malignancies in NF1 affected patients is estimated to be 5–15% higher than in the general population. We reviewed clinical aspects and genetic mechanisms of tumorigenesis in NF1 affected patients.

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Clinical Manifestations and Management of Neurofibromatosis Type 1

Cited by 199 publications

References 24 publications

126 novel mutations in Italian patients with neurofibromatosis type 1

126 novel mutations in Italian patients with neurofibromatosis type 1

Valosin-containing protein and neurofibromin interact to regulate dendritic spine density

The Neurofibromatosis type 1:A dominantly inherited tumors-predisposing disorder

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