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.
© 2023 International Society for Developmental Neuroscience.