These two authors contributed equally to this work.
SURF1-associated leigh syndrome: A case series and novel mutations†
Article first published online: 30 APR 2012
© 2012 Wiley Periodicals, Inc.
Volume 33, Issue 8, pages 1192–1200, August 2012
How to Cite
Lee, I.-C., El-Hattab, A. W., Wang, J., Li, F.-Y., Weng, S.-W., Craigen, W. J. and Wong, L.-J. C. (2012), SURF1-associated leigh syndrome: A case series and novel mutations. Hum. Mutat., 33: 1192–1200. doi: 10.1002/humu.22095
Communicated by Arnold Munnich
- Issue published online: 13 JUL 2012
- Article first published online: 30 APR 2012
- Accepted manuscript online: 4 APR 2012 04:26PM EST
- Manuscript Accepted: 15 MAR 2012
- Manuscript Received: 19 NOV 2011
- mitochondrial disorders;
- complex IV deficiency;
- complex IV assembly;
- electron transport chain;
- atypical Leigh syndrome
Leigh syndrome (LS) is a mitochondrial disease that typically presents in infancy with subacute neurodegenerative encephalopathy. It is genetically heterogeneous, but mutations in the complex IV assembly genes, particularly SURF1, are an important cause. In this study, SURF1 gene was sequenced in 590 patients with clinical suspicion of LS, complex IV deficiency, or clinical features of mitochondrial disorders. We identified 21 patients with clinical features of LS who are either homozygous or compound heterozygous for SURF1 mutations. Twenty-two different mutations were identified, including 13 novel mutations. Of the 42 mutant alleles, 36 (86%) are null mutations (frameshift, splicing, or nonsense) and 6 (14%) are missense. We have also reviewed the previously reported SURF1 mutations and observed a clustering of mutation in exon 8 of SURF1, suggesting a vital function for this region. Although mutations in SURF1 have been mainly associated with typical LS, five of the patients in this report had an atypical course of LS. There is no definite genotype–phenotype correlation; however, frameshift mutations resulting in protein truncation closer to the C-terminus may carry a better prognosis. Hum Mutat 33:1192–1200, 2012. © 2012 Wiley Periodicals, Inc.