Novel and recurrent mutations in theNF1 gene in Italian patients with neurofibromatosis type 1

Luca, Alessandro De; Schirinzi, Annalisa; Buccino, Anna; Bottillo, Irene; Sinibaldi, Lorenzo; Torrente, Isabella; Ciavarella, Angela; Dottorini, Tania; Porciello, Roberto; Giustini, Sandra; Calvieri, Stefano; Dallapiccola, Bruno

doi:10.1002/humu.9245

Cited by 48 publications

(49 citation statements)

References 33 publications

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“…Since no further nucleotide variations were detected with direct sequencing in the five DHPLC-negative probands, DHPLC revealed a100% sensitivity compared to that for direct sequencing, which is considered the gold standard in mutational analysis (Xiao and Oefner, 2001); however, DHPLC is much less laborious, time-consuming and expensive. Our results agree with data reported by other groups on DHPLC analysis performed on many other genes, such as BRCA (Gross et al, 1999), NF1 (De Luca et al, 2004), MLH1 and MSH2 (Holinski-Feder et al, 2001). Furthermore, our prospective DHPLC mutation detection rate (89.3%) is very similar to that obtained by direct sequencing on ENG and ALK1 by other groups (Letteboer et al, 2005;Schulte et al, 2005).…”

Section: Discussionsupporting

confidence: 92%

DHPLC-based mutation analysis of ENG and ALK-1 genes in HHT Italian population

et al. 2006

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Section: Discussionsupporting

confidence: 92%

DHPLC-based mutation analysis of ENG and ALK-1 genes in HHT Italian population

et al. 2006

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“…2002; De Luca et al. 2004, 2007), although the findings of an Italian mortality study were consistent with those performed in other industrialized countries (Zöller et al. 1995; Rasmussen et al.…”

Section: Discussionsupporting

confidence: 86%

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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“…Although no variants in the NF2 gene were detected, four heterozygous variants in the NF1 gene were identified. Two of these (c.2288T>C/p.L763P, c.574 C>T/p.R192*) were previously reported mutations [13][14][15], and the others (c.768delT/p. F256Lfs*25, c.2229_2230delTG/p.V744Qfs*23) were novel ( Figure 1A).…”

Section: Resultsmentioning

confidence: 99%

Identification of One <em>BOCR</em> Mutation and Five <em>NF1</em> Mutations in Male Patients with Neurofibromatosis Type 1 and Congenital Pseudarthrosis of the Tibia

Zhou¹,

Zeng

et al. 2016

Preprint

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Neurofibromatosis type1 (NF1) is an autosomal dominant disorder caused by mutations in the NF1gene. Although congenital pseudarthrosis of the tibia (CPT) has frequently been associated with NF1, the underlying molecular mechanism of CPT in these NF1 patients is yet ill-understood. The aim of the present study was to detect NF1 mutations from genomic DNA and to harbor variants associated with CPT in NF1 patients. Whole-exome sequencing was first carried out with samples from two patients with CPT in one NF1 family, and a novel mutation c.2324A>G (p.E775G) in NF1 gene was identified. Additionally, a missense variant c.455C>T (p.P152L) in BCOR gene completely co-segregated with the CPT phenotype within this family. Subsequently, NF1 and NF2 genes in four other unrelated patients with both NF1 and CPT were screened using targeted sequencing. Four mutations in NF1 gene, including two known mutations (c.2288T>C/p.L763P, c.574 C>T/p.R192*) and two novel mutations (c.768delT/p.F256Lfs*25, c.2229_2230delTG/ p.V744Qfs*23) were detected. Further study confirmed that CPT was present in NF1 families, and NF1 mutations were closely associated with these complex phenotypes. Moreover, the data from the current study indicated that male gender might be a susceptibility factor for CPT in NF1. Therefore, we speculated that BCOR variants might be related to CPT phenotype among male NF1 patients.

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Novel and recurrent mutations in theNF1 gene in Italian patients with neurofibromatosis type 1

Cited by 48 publications

References 33 publications

DHPLC-based mutation analysis of ENG and ALK-1 genes in HHT Italian population

DHPLC-based mutation analysis of ENG and ALK-1 genes in HHT Italian population

126 novel mutations in Italian patients with neurofibromatosis type 1

Identification of One <em>BOCR</em> Mutation and Five <em>NF1</em> Mutations in Male Patients with Neurofibromatosis Type 1 and Congenital Pseudarthrosis of the Tibia

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