Thirty-Nine Novel Neurofibromatosis 1 (<i>NF1)</i>Gene Mutations Identified in Slovak Patients

Nemethova, Martina; Bolcekova, Anna; Ilenčíková, Denisa; Ďurovčíková, Darina; Hlinkova, Katarina; Hlavatá, Anna; Kovács, László; Kádaši, Ľudevít; Zaťková, Andrea

doi:10.1111/ahg.12026

Cited by 28 publications

(30 citation statements)

References 72 publications

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“…4%: Valero et al (2011), 89.5%: Nemethova et al (2013), 96.3%: Sabbagh et al (2013)]. Hence, the performance of the presently reported protocol was comparable with that of the direct capillary sequencing methods.…”

Section: Discussionsupporting

confidence: 51%

“…Comparison of the distributions of nonsense, splice-site variants, and missense mutations in the Japanese population versus the northern European population, as reported by Messiaen et al (2000), Nemethova et al (2013), Sabbagh et al (2013), andValero et al (2011), revealed no statistically significant differences among the groups ( p = 0.203 using the Fisher exact test for countable data).…”

Section: Mutation Detectionmentioning

confidence: 72%

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The Use of Next-Generation Sequencing in Molecular Diagnosis of Neurofibromatosis Type 1: A Validation Study

Maruoka

Tamura

Torii

et al. 2014

Genetic Testing and Molecular Biomarkers

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Aims:We assessed the validity of a next-generation sequencing protocol using in-solution hybridization-based enrichment to identify NF1 mutations for the diagnosis of 86 patients with a prototypic genetic syndrome, neurofibromatosis type 1. In addition, other causative genes for classic genetic syndromes were set as the target genes for coverage analysis. Results: The protocol identified 30 nonsense, 19 frameshift, and 8 splice-site mutations, together with 10 nucleotide substitutions that were previously reported to be pathogenic. In the remaining 19 samples, 10 had single-exon or multiple-exon deletions detected by a multiplex ligationdependent probe amplification method and 3 had missense mutations that were not observed in the normal Japanese SNP database and were predicted to be pathogenic. Coverage analysis of the genes other than the NF1 gene included on the same diagnostic panel indicated that the mean coverage was 115-fold, a sufficient depth for mutation detection. Conclusions: The overall mutation detection rate using the currently reported method in 86 patients who met the clinical diagnostic criteria was 92.1% (70/76) when 10 patients with large deletions were excluded. The results validate the clinical utility of this next-generation sequencing-based method for the diagnosis of neurofibromatosis type 1. Comparable detection rates can be expected for other genetic syndromes, based on the results of the coverage analysis.

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Section: Discussionsupporting

confidence: 51%

Section: Mutation Detectionmentioning

confidence: 72%

The Use of Next-Generation Sequencing in Molecular Diagnosis of Neurofibromatosis Type 1: A Validation Study

Maruoka

Tamura

Torii

et al. 2014

Genetic Testing and Molecular Biomarkers

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show abstract

“…2000; Nemethova et al. 2013). In two patients, we obtained clinical evidence of segmental NF1, probably due to mosaicism (NF1_40 and NF1_122).…”

Section: Resultsmentioning

confidence: 99%

“…Indeed, higher detection rates were possible only with a multistep protocol, when analyses of DNA and RNA were integrated (Nemethova et al. 2013; Sabbagh et al. 2013) 95% was reached by Messiaen et al.…”

Section: Discussionmentioning

confidence: 99%

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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“…These include neurofibromatosis type 1, Rubinstein-Taybi syndrome, Cornelia de Lange syndrome, and Kleefstra syndrome [Roelfsema et al, 2005;Russo et al, 2012;Nemethova et al, 2013;Schwaibold et al, 2014]. These cases provide evidence that a partial duplication of ZEB2 could similarly result in a haploinsufficient condition.…”

Section: Discussionmentioning

confidence: 86%

A Novel Partial Duplication of ZEB2 and Review of ZEB2 Involvement in Mowat-Wilson Syndrome

Baxter

Vivian²,

Hagelstrom

et al. 2017

Mol Syndromol

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Mowat-Wilson syndrome is a rare genetic condition characterized by intellectual disability, structural anomalies, and dysmorphic features. It is caused by haploinsufficiency of the ZEB2 gene in chromosome 2q22.3. Over 180 distinct mutations in ZEB2 have been reported, including nonsense and missense point mutations, deletions, and large chromosomal rearrangements. We report on a 14-year-old female with a clinical diagnosis of Mowat-Wilson syndrome. Chromosomal microarray identified a novel de novo 69-kb duplication containing exons 1 and 2 of the ZEB2 gene. Sequence analysis identified no other variants in this gene. This is the first report of a partial duplication of the ZEB2 gene resulting in Mowat-Wilson syndrome.

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Thirty-Nine Novel Neurofibromatosis 1 (NF1)Gene Mutations Identified in Slovak Patients

Cited by 28 publications

References 72 publications

The Use of Next-Generation Sequencing in Molecular Diagnosis of Neurofibromatosis Type 1: A Validation Study

The Use of Next-Generation Sequencing in Molecular Diagnosis of Neurofibromatosis Type 1: A Validation Study

126 novel mutations in Italian patients with neurofibromatosis type 1

A Novel Partial Duplication of ZEB2 and Review of ZEB2 Involvement in Mowat-Wilson Syndrome

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