Abstract
The identified mutations in the G elongation factor mitochondrial 1 (GFM1) gene have been associated with heterogeneous clinical features of an early-onset mitochondrial disease in only 25 families. The present study reports the case of two siblings with a novel GFM1 variant and their clinical and laboratory presentations, which included progressive hepatic encephalopathy, failure to thrive and persistent lactic acidemia. Both histological changes and diminished expression of the GFM1 protein were observed in the liver and kidney tissues of the index patient. Whole-exome and Sanger sequencing technologies were used to diagnose the index patient with defective GFM1 using amniocentesis at 32 weeks' gestation. Heterozygous mutations in the GFM1 gene were identified in both siblings: A novel mutation, C1576T in exon 13 inherited from their asymptomatic mother, resulting in a premature stop codon at amino acid position 526 and the previously reported G688A mutation on the boundary between exon 5 and intron 5-6, inherited from their asymptomatic father. In conclusion, the present study reports two siblings carrying a novel GFM1 variant with a rare fatal mitochondrial disease.