Clinical and molecular characterization of neurofibromatosis in southern Brazil
| Autor: | Maievi Fonini, Patricia Ashton-Prolla, Filippo Vairo, Cristina Brinckmann Oliveira Netto, Clévia Rosset, Isabel Cristina Bandeira |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male congenital hereditary and neonatal diseases and abnormalities Heterozygote Neurofibromatosis 2 Neurofibromatosis 1 Adolescent Biology Pathology and Forensic Medicine 03 medical and health sciences otorhinolaryngologic diseases Genetics medicine Humans Neurofibromatosis type 2 Neurofibromatosis Child neoplasms Molecular Biology Gene Genotype-Phenotype Correlations Neurofibromatoses Neurocutaneous Syndromes Heterozygote advantage medicine.disease Phenotype eye diseases nervous system diseases 030104 developmental biology Molecular Medicine Female Multiplex Polymerase Chain Reaction Brazil |
| Zdroj: | Expert review of molecular diagnostics. 18(6) |
| ISSN: | 1744-8352 |
| Popis: | 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 NF1 and NF2 variants in patients from Southern Brazil.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 (NF1, RNF135, and SUZ12 genes) and NF2 (NF2 and SMARCB1 genes). Large rearrangements were assessed by Multiplex Ligation-dependent Probe Amplification.Sixty-eight heterozygous NF1 variants were identified in 75/93 probands (80%) and 3 heterozygous NF2 variants were identified in 3/7 probands (43%). In NF1, 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 NF2, all variants were pathogenic. No novel genotype-phenotype correlations were observed; however, previously described correlations were confirmed in our cohort.The clinical and molecular characterization of neurofibromatoses in different populations is very important to provide further insights into the pathogenesis of these diseases. |
| Databáze: | OpenAIRE |
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