{Reference Type}: Case Reports
{Title}: Expanding the phenotype of mitochondrial disease: Novel pathogenic variant in ISCA1 leading to instability of the iron-sulfur cluster in the protein.
{Author}: Lebigot E;Hully M;Amazit L;Gaignard P;Michel T;Rio M;Lombès M;Thérond P;Boutron A;Golinelli-Cohen MP;
{Journal}: Mitochondrion
{Volume}: 52
{Issue}: 0
{Year}: 05 2020
{Factor}: 4.534
{DOI}: 10.1016/j.mito.2020.02.008
{Abstract}: We report a patient carrying a novel pathogenic variant p.(Tyr101Cys) in ISCA1 leading to MMDS type 5. He initially presented a psychomotor regression with loss of gait and language skills and a tetrapyramidal spastic syndrome. Biochemical analysis of patient fibroblasts revealed impaired lipoic acid synthesis and decreased activities of complex I and II of respiratory chain. While ISCA1 is involved in the mitochondrial machinery for iron-sulfur cluster biogenesis, these dysfunctions are secondary to impaired maturation of mitochondrial proteins containing the [4Fe-4S] clusters. Expression and purification of the human ISCA1 showed a decreased stability of the [2Fe-2S] cluster in the mutated protein.