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SURF1-associated leigh syndrome: A case series and novel mutations

Authors

  • Inn-Chi Lee,

    1. Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan
    2. Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan
    3. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
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    • These two authors contributed equally to this work.

  • Ayman W. El-Hattab,

    1. Division of Medical Genetics, Department of Child Health, University of Missouri Health Care, Columbia, Missouri
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    • These two authors contributed equally to this work.

  • Jing Wang,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
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  • Fang-Yuan Li,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
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  • Shao-Wen Weng,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung, Taiwan
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  • William J. Craigen,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
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  • Lee-Jun C. Wong

    Corresponding author
    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    • Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030.
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  • Communicated by Arnold Munnich

Abstract

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.

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