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

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Kocabey M., Özkalaycı H., Çankaya T., Yılmaz Uzman C., Çağlayan A. O., Ülgenalp A., ...More

International Journal of Developmental Neuroscience, vol.83, no.5, pp.456-465, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 83 Issue: 5
  • Publication Date: 2023
  • Doi Number: 10.1002/jdn.10278
  • Journal Name: International Journal of Developmental Neuroscience
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.456-465
  • Keywords: cafe au lait macules, early diagnosis, genotype–phenotype correlation, neurofibromatosis type 1, NF1
  • Dokuz Eylül University Affiliated: Yes


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.