Clinical Findings and Mutation Analysis of Nf1 Patients in Turkey

Abstract

Neurofibromatosis type 1 (NF1) is an autosomal dominant disease that is caused by mutations of the NF1 gene. NF1 is clinically characterized by neurofibromas, pigmentation anomalies, and an increased risk of malignant tumors. The mutation rate of NF1 is one of the highest known for human disorders: approximately 50% of all affected individuals are sporadic cases and carry de novo mutations Therefore mutation analysis of NF1 may be an important tool in early diagnosis and genetic counseling. This is the first large NF1 study performed in Turkey. The data collected in this study enabled us to overview the genetic and clinical aspects of NF1 molecular diagnostics. The patients, who were clinically diagnosed for NF1, were included in this study. These patients were clinically evaluated, and subgroup of them genotyped or DNA sequenced for mutations in NF1, either to confirm the clinical diagnosis or to identify pathogenic mutations. The mutation detection rate was 52%, based on analysis of only genomic DNA. We observed that frameshift mutations were the largest proportion of the identified mutations (38.5%). The frequency of microdeletions was 26.9% and the splice site and nonsense mutations were 11.5% in this cohort. Turkish NF1 patients have similar NF1 germline mutations compared to other populations. Considering that some of these detected mutations belonged to the patients who did not fulfill the NIH criteria for NF1 diagnosis, mutation analysis of NF1 is an important tool in early diagnosis and genetic counseling.