Objective: To catalog and correlate the clinical features and mutational spectrum of neurofibromatosis type 1 (NF1) patients attending a tertiary care center in India.
Methods: NF1 patients with confirmed molecular diagnosis from 2014 to 2021 were included in the study. The molecular tests used for the diagnosis were exome sequencing, targeted gene sequencing, and Multiple Ligation Probe Assay.
Results: Forty-two clinically diagnosed NF1 patients who had confirmed molecular diagnosis, which is now part of the revised diagnostic criteria, were included in the analysis. Nonsense variants were the most frequently observed (35.71%), followed by frameshift (23.8%), splice site (14.29%), deletion (11.9%), missense (9.5%), and in-frame deletions (4.76%) in our case series. Three variants (c. 5269-1G > C, c. 1541_1542del AG, and c. 6853_6854insA) were identified in more than one patient, suggesting that the variants are widely distributed in the gene and lack any mutational hotspot. This study supports the previous findings that patients with the variant c. 2970_2972delAAT do not develop neurofibromas; however, it was not necessary for those with whole gene deletion to have dysmorphic features as reported by other studies. The study could not establish any correlation between the type of variants and specific clinical features. Around 28% of mutations could be identified by screening exons 14, 28, 37, 46 and intron 37 in this population.
Conclusion: This study will contribute to a better understanding of the phenotypic variability of neurofibromatosis patients. The variable expressivity seen in NF1 suggests that modifying genes may be involved in the development of particular clinical features in addition to NF1 mutations.
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