Clinical and molecular characterization of neurofibromatosis in southern Brazil

<b>Objectives</b>: Neurofibromatoses (type 1: NF1; type 2: NF2) are autosomal dominant tumor predisposition syndromes mostly caused by loss-of-function mutations in the tumor suppressor genes NF1 and NF2, respectively. Genotyping is important for correct diagnosis of these diseases. The authors aimed to characterize <i>NF1</i> and <i>NF2</i> variants in patients from Southern Brazil. <b>Methods</b>: Ninety-three unrelated probands with NF1 and 7 unrelated probands with NF2 features were recruited from an Oncogenetics center in Southern Brazil. Two next generation sequencing panels were customized to identify point mutations: NF1 (<i>NF1, RNF135</i>, and <i>SUZ12</i> genes) and NF2 (<i>NF2</i> and <i>SMARCB1</i> genes). Large rearrangements were assessed by Multiplex Ligation-dependent Probe Amplification. <b>Results</b>: Sixty-eight heterozygous <i>NF1</i> variants were identified in 75/93 probands (80%) and 3 heterozygous <i>NF2</i> variants were identified in 3/7 probands (43%). In <i>NF1</i>, 59 (87%) variants were pathogenic (4 large rearrangements – 6%), 6 (9%) were likely pathogenic, 3 (4%) were variants of uncertain significance and 28 (41%) were novel. In <i>NF2</i>, all variants were pathogenic. No novel genotype-phenotype correlations were observed; however, previously described correlations were confirmed in our cohort. <b>Conclusion</b>: The clinical and molecular characterization of neurofibromatoses in different populations is very important to provide further insights into the pathogenesis of these diseases.