Loss-of-function mutations of SURF-1 are specifically associated with Leigh syndrome with cytochrome c oxidase deficiency
Articolo
Data di Pubblicazione:
1999
Citazione:
Loss-of-function mutations of SURF-1 are specifically associated with Leigh syndrome with cytochrome c oxidase deficiency / V. Tiranti, M. Jaksch, S. Hofmann, C. Galimberti, K. Hoertnagel, L. Lulli, P. Freisinger, L. Bindoff, K.D. Gerbitz, G. Comi, G. Uziel, M. Zeviani, T. Meiringer. - In: ANNALS OF NEUROLOGY. - ISSN 0364-5134. - 46:2(1999), pp. 161-166.
Abstract:
Mutations of SURF-1, a gene located on chromosome 9q34, have recently been identified in patients affected by Leigh syndrome (LS), associated with deficiency of cytochrome c oxidase (COX), the terminal component of the mitochondrial respiratory chain. To investigate to what extent SURF-1 is responsible for human disorders because of COX deficiency, we undertook sequence analysis of the SURF-1 gene in 46 unrelated patients. We analyzed 24 COX-defective patients classified as having typical Leigh syndrome (LSC(COX)), 6 patients classified as Leigh-like (LL(COX)) cases, and 16 patients classified as non-LS(COX) cases. Frameshift, stop, and splice mutations of SURF-1 were detected in 18 of 24 (75%) of the LS(COX) cases. No mutations were found in the LL(COX) and non-LS(COX) group of patients. Rescue of the COX phenotype was observed in transfected cells from patients harboring SURF-1 mutations, but not in transfected cell lines from 2 patients in whom no mutations were detected by sequence analysis. Loss of function of SURF-1 protein is specifically associated with LS(COX), although a proportion of LS(COX) cases must be the result of abnormalities in genes other than SURF-1. SURF-1 is the first nuclear gene to be consistently mutated in a major category of respiratory chain defects. DNA analysis can now be used to accurately diagnose LS(COX), a common subtype of Leigh syndrome.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
nuclear; common
Elenco autori:
V. Tiranti, M. Jaksch, S. Hofmann, C. Galimberti, K. Hoertnagel, L. Lulli, P. Freisinger, L. Bindoff, K.D. Gerbitz, G. Comi, G. Uziel, M. Zeviani, T. Meiringer
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