Retrospective study of molecular analysis results in cases diagnosed with rasopathy

Aim: Rasopathies are one of the most common genetic syndrome groups. Clinical findings may be overlapped in some cases and molecular diagnosis has a great importance for this purpose. Targeted gene panels are very important as a fast and cost-effective diagnostic method. In this thesis, it is aimed to determine the frequency of syndromes and mutation types and to associate them with the clinical findings, to interpret the results with genotype-phenotype correlations by retrospectively investigating Rasopathies according to targeted next-generation sequence analysis data. Material and method: For this thesis study, 61 cases who applied to İnönü University Faculty of Medicine Medical Genetics Polyclinic between the years 2016-2021 and were diagnosed with Rasopathy molecularly were analyzed retrospectively. Descriptive statistical methods were used for the study data. Results: In the study, 41 pathogenic, 17 likely pathogenic and 3 VUS variants were detected according to ACMG criteria. 20 novel variants were detected, 19 of which were found in the NF1 gene. Totally, 41 variants have been previously reported in the literature. A variant in NF1 gene was detected in 42 of the index cases. Clinically related variants were found in PTPN11 gene in 9 cases, RAF1 in 3 cases, SOS1 in 3 cases, KRAS in a case, NRAS in a case, SOS2 in a case and RIT1 in a case. Conclusion: In our study, cases with a molecular diagnosis of Rasopathy were investigated retrospectively and evaluated in terms of clinical correlations. In terms of distribution rates of rasopathies, NF1 was the most common and Noonan syndrome was the second most common. Molecular analysis is very important, especially in cases that clinical differential diagnosis among Rasopathies cannot be made. Designed targeted Rasopathy panel tests save time and money and facilitate diagnosis.