Investigation of MECP2 Gene Variants with Next Generation Sequencing in Classic Rett Syndrome Clinical Cases
Project no. 20429 · Status: Kapanmış · 2019
Summary
Objective: Rett syndrome (RTT) is a progressive neurodevelopmental disorder that usually occurs due to MECP2 gene mutations and primarily affects girls. In patients with normal development for the first 6 months, symptoms such as walking anomalies, loss of speech, respiratory disorders and recurrent meaningless hand movement occur after the sixth month. In the later stages of the disease, patients may experience decreased head growth, autistic facial appearance, cardiac anomalies, autonomic nervous system disorders and seizures. There are two phenotypical subtypes of RTT in the clinic, classical (typical) and variant (atypical). In classical RTT, MECP2 gene mutations are responsible for approximately 95% of cases. In this study, it was aimed to investigate the mutations in the MECP2 gene with the next generation sequencing in 20 patients who are clinically considered to be diagnosed with Classic Rett Syndrome, to create a resource to improve the diagnosis and follow-up possibilities of Turkish society, and to contribute to the Turkish and world literature. Material and method: Exonic regions and exon-intron junctions of the MECP2 gene were sequenced using next generation sequencing in 20 cases diagnosed as Classical Rett followed by Ege University Faculty of Medicine, Department of Pediatric Neurology and Pediatric Genetic Diseases. The pathogenic variants were confirmed by Sanger sequencing. Results: Point mutations was detected in the MECP2 gene, which describes the classic Rett syndrome in two different cases. Conclusion: Consequently, this study contributed to the medical literature from our country and university as the first whole MECP2 gene sequencing study with the next generation sequencing technology in Turkish society. In addition, detailed genetic counseling was given to the families of the cases with pathogenic variants and prenatal diagnosis opportunities were presented to the families for next pregnancies. Keywords: Rett syndrome; MECP2; next generation sequencing