Türkiye'deki akraba evliliklerine bağlı nörogenetik hastalık yükünün araştırılmasında yeni genomik yaklaşımlar

Consanguineous marriages are common in Turkey and carry an increased risk of genetic conditions with autosomal recessive inheritance. The nervous system and muscle are affected by these conditions leading to severe disability or premature death. While each condition is individually rare, there are several hundred genetically defined neurogenetic disease entities, collectively resulting in significant health and economic burden. A definitive molecular diagnosis has not been achieved for most of the children with neurogenetic conditions in Turkey, as infrastructure and access to sophisticated diagnostic options such as MRI, comprehensive metabolic testing, muscle biopsies and genetic testing are limited. The advance of next-generation sequencing now offers the opportunity to understand the genetic causes of childhood neurogenetic disorders better, ultimately providing a definite diagnosis for many families, and in some cases effective treatments. In this study, children with undiagnosed neurogenetic disorders born to consanguineous parents were recruited to the study. Disease-causing variants were identified through systematic deep phenotyping of neurogenetic patients from consanguineous families, combined with whole exome sequencing (WES). Variants were analyzed through RD-Connect Genome-Phenome Analysis Platform (GPAP) and assessed for predicted deleterious effects with the integration of data from several bioinformatics tools. WES provided a molecular diagnosis for 62 families out of 138 (45%). This study will help to develop new prevention and treatment strategies, improved outcomes for affected families, and to an essential body of genomic data relevant to the population and increased genomics research capacity within the Turkish medical community.