Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Aug;83(5):456-465.
doi: 10.1002/jdn.10278. Epub 2023 Jun 6.

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

Mehmet Kocabey  1 , Hande Özkalaycı  1 , Tufan Çankaya  1 , Ceren Yılmaz Uzman  2 , Ahmet Okay Çağlayan  1 , Ayfer Ülgenalp  1 , Murat Derya Erçal  2
Affiliations

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

Mehmet Kocabey et al. Int J Dev Neurosci. 2023 Aug.

Abstract

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.

Keywords: NF1; cafe au lait macules; early diagnosis; genotype-phenotype correlation; neurofibromatosis type 1.

PubMed Disclaimer

References

REFERENCES

    1. Anastasaki, C., Gao, F., & Gutmann, D. H. (2019). Commentary: Identification of mutation regions on NF1 responsible for high- and low-risk development of optic pathway glioma in Neurofibromatosis type I. Frontiers in Genetics, 10, 115. https://doi.org/10.3389/fgene.2019.00115
    1. Bettegowda, C., Upadhayaya, M., Evans, D. G., Kim, A. R., Mathios, D., Hanemann, C. O., & on behalf of the REiNS International Collaboration. (2021). Genotype-phenotype correlations in Neurofibromatosis and their potential clinical use. Neurology, 97(7 Suppl 1), S91-S98. https://doi.org/10.1212/WNL.0000000000012436
    1. Castellanos, E., Rosas, I., Negro, A., Gel, B., Alibés, A., Baena, N., Pineda, M., Pi, G., Pintos, G., Salvador, H., Lázaro, C., Blanco, I., Vilageliu, L., Brems, H., Grinberg, D., Legius, E., & Serra, E. (2020). Mutational spectrum by phenotype: Panel-based NGS testing of patients with clinical suspicion of RASopathy and children with multiple café-au-lait macules. Clinical Genetics, 97(2), 264-275. https://doi.org/10.1111/cge.13649
    1. ClinVar database NF1 (n.d.). Available at: https://www.ncbi.nlm.nih.gov/clinvar/?term=NF1[sym] (Accessed: 5 March 2022).
    1. Ece Solmaz, A., Isik, E., Atik, T., Ozkinay, F., & Onay, H. (2021). Mutation spectrum of the NF1 gene and genotype-phenotype correlations in Turkish patients: Seventeen novel pathogenic variants. Clinical Neurology and Neurosurgery, 208, 106884. https://doi.org/10.1016/j.clineuro.2021.106884

Supplementary concepts

LinkOut - more resources