Expanding the phenotype of mitochondrial disease: Novel pathogenic variant in ISCA1 leading to instability of the iron-sulfur cluster in the protein.
Mitochondrion
; 52: 75-82, 2020 05.
Article
en En
| MEDLINE
| ID: mdl-32092383
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Sustitución de Aminoácidos
/
Enfermedades Mitocondriales
/
Proteínas Mitocondriales
/
Proteínas Hierro-Azufre
Límite:
Child, preschool
/
Humans
/
Male
Idioma:
En
Revista:
Mitochondrion
Año:
2020
Tipo del documento:
Article