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

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.