Respiratory chain defects in hereditary spastic paraplegias.
Hereditary Spastic Paraplegias (HSPs) are heterogeneous neurodegenerative disorders whose etiopathogenesis is still unclear. The identification of pathogenic mutations in a gene (SPG7) encoding a mitochondrial metalloprotease suggested that oxidative phosphorylation (OXPHOS) alterations might underlie HSP in a subgroup of patients. We performed clinical, morphological, biochemical, and molecular genetic studies in six HSP patients and in six sporadic patients to investigate OXPHOS in muscle biopsies. Complicated and pure forms were included in our study. Morphological alterations of the type seen in OXPHOS-related disorders were found in three patients. Five patients showed an isolated defect of complex I activity. No mutations in the SPG7 gene were detected. Our results suggest that OXPHOS defects in HSP patients are more common than previously believed.
Piemonte
F
F
Molecular Medicine and Neurology, IRCCS-Ospedale Bambino Gesù, Piazza S. Onofrio 4, 00165 Rome, Italy.
Casali
C
C
Carrozzo
R
R
Schägger
H
H
Patrono
C
C
Tessa
A
A
Tozzi
G
G
Cricchi
F
F
Di Capua
M
M
Siciliano
G
G
Amabile
G A
GA
Morocutti
C
C
Bertini
E
E
Santorelli
F M
FM
D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002648:Child; D004579:Electron Transport / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D010085:Oxidative Phosphorylation; D010264:Paraplegia / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D010375:Pedigree