Novel genetic causes and functional studies of severe neurological and multi-organ diseases in children

Undefined severe neurological and multi-organ diseases are rare as single diseases, but as a group of diseases, they are responsible for significant morbidity, impaired quality of life and mortality, emphasizing the importance of neuroscience research and its translation into novel diagnostic and treatment strategies. Molecular karyotyping and whole-exome sequencing were used to identify three novel disease-causing genes, GLE1, NHLRC2 and MYH7B, in Northem Finnish families having children with undefined progressive neuromuscular diseases. Functional studies on GLE1, NHLRC2, and MYH7B were conducted in order to understand better the impact of these mutations. The studies revealed that the cellular localization of GLE1 was impaired due to a mutation in the coding gene. The NHLRC2 is involved in many biological processes and its dysfunction has a role in the development of a novel FINCA disease and in fibrosis. Furthermore, mutations in MYH7B in the myosin family have now been connected to encephalomyopathies. Mutations in GLE1, NHLRC2 and MYH7B are involved in encephalomyopathies and neurodegeneration, stressing the important role of these genes in normal psychomotor development Analyses of these previously uncharacterized disease-causing gene mutations provided new insights into the etiologies behind these diseases, representing a relevant starting point for resolving the pathomechanisms underpinning these disorders. The newly-discovered human disease-causing genes and the novel phenotypes of childhood onset neuromuscular diseases provide the possibility for offering the relevant families preclinical diagnostics and may be beneficial in the identification of similar clinical phenotypes all around the world. ; Tiivistelmä Yksittäiset, määrittelemättömät, vaikeat neurologiset monielinsairaudet ovat harvinaisia. Sen sijaan neurologisten ja monielinsairauksien alle ryhmittyvät taudit ovat merkittävä syy useisiin sairauksiin, jotka heikentävät elämänlaatua ja aiheuttavat kuolleisuutta. Tästä johtuen ...