Özet:

Objective: Neurofibromatosis Type 1 (NF1) is a common autosomal dominant genetic disorder that has a variable phenotype. The genetic causes of clinical variability of NF1 patients are questioned. DNA repair genes are responsible for proofreading the missing in the DNA. We aimed to analyze the expression of DNA repair genes and their clinical significance in NF1 patients; comparing the existence of neurofibroma or hamartomatous lesions or other tumours or existence of NF1 in the family. The other purpose of this study was to determine whether any relationship between gene expressions and clinical findings. Methods: NF1 patients and malignancy with NF1 patients were included in this study. In the control gruop children that they are in the similar age group and they have no disease and no malignity group were included. This study included a total of 46 cases. 36 NF1 patients (30 children; 6 parents), 8 control cases without any disease, two control cases with rhabdomyosarcoma without NF1 were included in this study. The average age of control group was 17 ± 7.03 (10-30 age) (median 13 age). In the NF1 suffints gruop 17 of them are female, and 19 are male. The average age at diagnosis is 10.08 ± 8.86 (9 months- 38 age)(median age 8) for children and 40.50 ± 1.22 (39-42 age) (median age 40) for parents. Among 36 patients, 17 had neurofibromas, 17 had hamartomatous lesions. Rhabdomyosarcoma (RMS) was observed in one patient, breast cancer in one patient and four patients suffered optical glioma. Peripheral blood was obtained from each case and mononuclear cells were separated. After RNA isolation and cDNA converting, expressions of 84 genes related with DNA Repair in standard array (SABiosciences) were determined by Real-Time PCR for each case. Fold changes and p values compared with control groups and fold changes evaluated with T test and p value in the comperative groups. Results: 36 NF1 patients, 8 healthy children as a control and 2 cases no NF1 relationship with malignancy (rhabdomyosarcoma) were included in the study group. In NF1 cases PNKP, RAD18, XAB2, XRCC3, XRCC4 and XRCC5 genes were downregulated compared with control group. In NF1 cases having neurofibromas, POLB was over expressed; while ERCC3, LIG1, MGMT, MRE11A, MPG, MSH6, PARP2, PRKDC, RAD51B, RAD52, RPA3, SMUG1, TREX1, UNG were downregulated compared with the NF1 cases without neurofibromas (p<0.05, T test). RAD18 is the downregulated and statistical significant gene for the existence of NF1 in the family. There are gen expression fold change differences determined when malignant tumor cases with/without NF1 were compared. DDB2, MGMT, MLH1, POLB UNG, XPA are increased. Conclusion: Our results may point toward a role of gene expression changes of DNA repair system to be predictive for clinical manifestations in NF1 cases

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