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GRACILE syndrome stands for: Growth retardation, aminoaciduria, cholestasis, iron overload, lactic acidosis, and early death. GRACILE syndrome begins during the gestation period. At most, those with the syndrome survive no more than a few months. The frequency is predicted to be 1 in 47,000 infants and found mostly in Finland. This is an autosomal recessive disease.

A mutation in the BCS1L gene is the cause for GRACILE syndrome. The BCS1L gene is responsible for the production of the production of the BCS1L protein found in the mitochondria, which is connected to the process of oxidative phosphorylation. In particular, the protein is a key contributor in the formation of complex III that is part of the electron transport chain. Complex III is still able to be produced, but it is reduced compared to a person without GRACILE syndrome. The deficiency of Complex III is more pronounced in the liver and kidneys.

Diagnosis: Genetic testing can be done prior to birth. There are currently 55 biochemical and molecular genetics tests that can be done to diagnose GRACILE syndrome. These tests include enzyme assays, deletion/duplication analysis, targeted variant analysis, sequence analysis of select exons, and sequence analysis of the entire coding region.

Other names: Fellman syndrome, Finnish lactic acidosis with hepatic hemosiderosis, and Finnish lethal neonatal metabolic syndrome.

Protofection (Protein-mediated transfection)

Originally, there was a technology to remove and replace human mitochondrial genome, using a lambda phage virus as the vector. They were able to transfect mitochondria that lacked mtDNA, with the entire human mitochondria genome. This process is called mitofection. This technology has been improved by adding a protein transduction system that transports/directs the mtDNA to the mitochondria in the target cells.

Protofection can deliver the entire mtDNA genome, PCR-generated fragments, mutations, or deletions.

Using Protein Transduction Domain (PTD) - Mitochondrial localization sequences (MLS) - Mitochondrial transcription fractor A (TFAM) technology it is possible to deliver mitochondrial genomes to cells.

PTD's are small regions of proteins that can cross the cell membrane freely. MLS are needed for the import of the mtDNA into the mitochondria. TFAM is the first isolated and cloned transcription factor for mtDNA. TFAM is responsible for binding to the mtDNA and unwinding it, which is critical for mtDNA replication.