Türkiye'de akraba evliliğine bağlı nörogenetik hastalıkların temelinde yatan mitokondriyal etiyolojinin sıklığı

Neurogenetic diseases are conditions that affect the brain, spinal cord, nerves and muscles. Neurogenetic diseases can be categorized as single gene disorders with autosomal, X-linked or mitochondrial inheritance, polygenic disorders, multifactorial disorders and disorders caused by inherited or de novo chromosomal abnormalities. Due to complicated clinical features and genetic heterogeneity of them and limitations in traditional diagnostic approaches, neurogenetic diseases are difficult to diagnose. Advances in the next-generation sequencing (NGS) technologies facilitate the molecular diagnosis and the discovery of novel disease genes and variants. Today, high-throughput, cost and time-effective whole exome sequencing (WES) is mostly preferable strategy used in diagnostic process of genetic diseases including neurogenetic diseases. In the frame of this project, 191 consanguineous families with childhood neurogenetic disorders were recruited and deeply phenotyped. To date, 138 of them underwent WES and causative genetic defect for 79 of them were identified with diagnostic yield of 57%. Among identified genes, 28 of them are known variants and 32 of them are novel candidate variants in known disease genes which are already associated with neurogenetic diseases and 15 of them are novel candidate genes. Importantly, mitochondrial function associated genes were higher than expected. By obtaining a diagnostic yield of 57% in such a large cohort, we showed the diagnostic utility of WES in neurogenetic diseases, identified novel candidate disease genes and variants by explaining genotype-phenotype relations in detail and provided genetic counseling and disease-specific therapies for some of the families. Keywords: NGS, WES, neurogenetic diseases, mitochondrial, consanguineous families