Neurological comorbidities and novel mutations in Turkish cases with neurofibromatosis type 1.

BACKGROUND AND PURPOSE: Neurofibromatosis type 1 (NF1) is a rare, autosomal dominant multisystemic disease. The NF1 gene is localized on chromosome 17q11.2. Patients with NF1 have different clinical presentations and comorbidities. The aim of the present study is to determine the novel mutations and neurological comorbidities of NF1.

METHODS

Patients who were diagnosed with NF1 by clinical criteria of the National Institutes of Health were included in the study. After a detailed examination, the NF1 gene was analysed with the help of next generation sequencing technology from peripheral blood samples via MiSeq (Illumina, USA). Bioinformatic analyzes were performed to evaluate the clinical significance of the detected variants via the international databanks in accordance with the ACMG (American College of Medical Genetics) guideline. In addition, cerebral-spinal MRI, cerebral angiography, and ENMG examinations were performed if deemed necessary.

RESULTS

Twenty patients (12 female, 8 male) were included in the study. The mean age was 25.8±10 (10-56) years. Previously defined 13 different pathogenic mutations according to the ACMG criteria were identified in 18 patients. Also, two novel mutations were detected in 2 cases. Moreover, neurological comorbidities (moyamoya disease, multiple sclerosis, Charcot Marie Tooth Type 1A) were found in 3 patients with NF1.

CONCLUSION

In the present study two novel mutations and three different neurological comorbidities were identified in NF1.