Mutation spectrum of the NF1 gene and genotype–phenotype correlations in Turkish patients: Seventeen novel pathogenic variants

Solmaz, Aslı Ece; Işık, Esra; Atik, Tahir; Özkınay, Ferda; Önay, Hüseyin

doi:10.1016/j.clineuro.2021.106884

Cited by 5 publications

(2 citation statements)

References 25 publications

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“…The variant detection rate in our study group was 56% (28/50) and it was 71.4% (25/35) within the index patients. This rate is similar to recent case series from Turkey, which reported diagnostic rates of 66.7%, 72.4%, 80.7% and 81.4% excluding cases with large deletions (Ece Solmaz et al, 2021; Güneş et al, 2021; Sharifi et al, 2021; Ulusal et al, 2017). Based on family history, 12 of the 25 (48%) patients with detected variants were the first affected patients in their respective families.…”

Section: Discussionsupporting

confidence: 90%

Genetic evaluation of 50 Turkish patients with neurofibromatosis type 1: 2 years experience of a single center

Kocabey

Özkalaycı

Çankaya

et al. 2023

Intl J of Devlp Neuroscience

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Background/aim Neurofibromatosis type 1 is an autosomal dominant neurocutaneous disorder. Clinical diagnosis is difficult in early childhood, and it is possible to miss a critical interval for tumour screening. In this study, we aimed to characterize the mutational spectrum of Turkish patients and discuss the benefits of molecular testing. Material and methods Fifty individuals from 35 unrelated families were included. Main referral reasons for genetic testing were as follows: to confirm a clinical diagnosis, to use in differential diagnosis and to evaluate first‐degree family member of a known patient. Two‐step process consisting of initial next generation sequencing of the NF1 gene and consequent multiplex ligation‐dependent probe amplification were performed. Results We identified a total of 30 variants in 28 individuals. Variant detection rate was 56% in the entire study group and 71.4% within the index patients. Four novel variants were found. Truncating variants constituted 60% of the entire mutation spectrum. A deletion or duplication was not detected. The most common feature was cafe au lait macules in 70% of the patients, followed by focal areas of signal intensity on brain imaging (26%), cutaneous neurofibromas (24%) and axillary freckling (24%). Conclusions Early sequencing in all suspected patients followed by deletion/duplication analysis in patients meeting clinical criteria and a case‐to‐case based consideration for RNA studies seems to be the effective algorithm for NF‐1 diagnosis.

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Section: Discussionsupporting

confidence: 90%

Genetic evaluation of 50 Turkish patients with neurofibromatosis type 1: 2 years experience of a single center

Kocabey

Özkalaycı

Çankaya

et al. 2023

Intl J of Devlp Neuroscience

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“…The studies included case analysis and multiple case analysis, mainly for NF1 gene mutation, with various types of mutation, including point mutation, frameshift mutation, splice site mutation, exon mutation, chimeric mutation and de novo mutation. All reported autosomal dominant inheritance [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] . DISCUSSION Neurofibromatosis type 1 is a multisystem genetic disease with more than 3000 NF1-related pathogenic variants reported, but pathogenic variants in exon 33 are extremely underrepresented.…”

Section: Resultsmentioning

confidence: 99%

Identifying a novel frameshift pathogenic variant in a Chinese family with neurofibromatosis type 1 and review of literature

X¹,

Wang²,

Wang³

2023

Int J Ophthalmol

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AIM: To detect the pathogenic gene variant in a family with neurofibromatosis type 1 (NF1). METHODS: This patient with NF1 was sequenced using target sequence capture and high-throughput sequencing technology. After detecting the suspicious pathogenic variant type, the pathogenic variant sites of the patient and the patient’s family members were verified by multiple ligation dependent probe amplification and Sanger sequencing. Sift, polyphen-2, Mutation Taster and GERP++ software were used to predict the pathogenicity of the unknown loci. The clinical data, diagnosis and treatment process of the patients were reviewed. Using the keyword “NF1; frameshift pathogenic variant”, relevant literature was gathered for analysis from Chinese and international databases, with articles dating from the establishment of each database to April 2022. RESULTS: A heterozygous frameshift pathogenic variant of NF1 in exon 33 was detected in the patient. The insertion of adenine in coding region 4486 resulted in the replacement of isoleucine with asparagine in protein 1497. Sanger sequencing validation and segregation analysis were performed, which demonstrated that the NF1 gene was cosegregated with the disease phenotype in this family. This study identified a novel NF1 heterozygous frameshift mutation c.4486dupA (p.I1497Nfs*12). Relevant literature retrieval found 7 Chinese articles and 12 foreign articles. With NF1 gene mutation, mutation types are diverse, including point mutation, frameshift mutation, splice site mutation, exon mutation, chimeric mutation and de novo mutation. Foreign reports are based on autosomal dominant inheritance. CONCLUSION: This study’s results demonstrate that a novel deletion in exon 33 caused NF1 in this Chinese family, expanding the mutational spectrum of the NF1 gene.

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A Comprehensive Overview of NF1 Mutations in Iranian Patients

Savad,

Modarressi,

Younesi

et al. 2024

Neuromol Med

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Mutation spectrum of the NF1 gene and genotype–phenotype correlations in Turkish patients: Seventeen novel pathogenic variants

Cited by 5 publications

References 25 publications

Genetic evaluation of 50 Turkish patients with neurofibromatosis type 1: 2 years experience of a single center

Genetic evaluation of 50 Turkish patients with neurofibromatosis type 1: 2 years experience of a single center

Identifying a novel frameshift pathogenic variant in a Chinese family with neurofibromatosis type 1 and review of literature

A Comprehensive Overview of NF1 Mutations in Iranian Patients

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