MYO5B in health and disease

Most people take eating and growing for granted. However, there are people with rare diseases who cannot tolerate dietary nutrients. These people require daily intravenous nutrition from birth and throughout their lives to grow and survive. Most people with these diseases do not live long because of life-threatening complications from long-term intravenous nutrition. One of these complications is liver failure. In this thesis, we studied the gene that, when mutated, is responsible for one of these diseases. We found that mutations in this gene, called MYO5B, can also affect cells in the liver. This means that in some patients with mutations in the MYO5B gene, liver failure may be due not only to intravenous nutrition but also to their genetic mutation. We have shown why some mutations in the MYO5B gene do affect liver cells and other mutations in the same gene do not, and we have provided a molecular explanation for this. In addition, we discovered that another food intolerance-associated gene, called UNC45A, is linked at the molecular level to the MYO5B gene, bringing two rare diseases together. The research described in this thesis increases our knowledge about the relationships between genetic mutations and symptoms in patients with these rare diseases and thus contributes to the understanding of clinical decision-making about disease progression.