Published online before print September 21, 2005, doi:10.1212/01.wnl.0000182814.55361.70)
NEUROLOGY 2005;65:1493-1495
© 2005 American Academy of Neurology
Brief Communications
POLG mutations in Alpers syndrome
K. V. Nguyen, PhD,
E. Østergaard, MD, PhD,
S. Holst Ravn, MD,
T. Balslev, MD,
E. Rubæk Danielsen, PhD,
A. Vardag, MD,
P. J. McKiernan, MD,
G. Gray, MD and
R. K. Naviaux, MD, PhD
From the Departments of Medicine (Drs. Nguyen and Naviaux) and Pediatrics (Dr. Naviaux), University of California, San Diego, and Mitochondrial and Metabolic Disease Center, San Diego, CA; John F. Kennedy Institute (Dr. Østergaard), Glostrup, Denmark; Departments of Genetics and Pediatrics (Dr. Holst Ravn), Rigshospitalet, Copenhagen, Denmark; Department of Paediatrics (Dr. Balslev), Skejby Hospital, Aarhus University Hospital, Denmark; Department of Radiology (Dr. Rubæk Danielsen), University of Copenhagen, Rigshospitalet, Denmark; Pediatric Critical Care Medicine (Dr. Vardag), West Boca Medical Center, Boca Raton, FL; Children's Hospital NHS Trust (Dr. McKiernan), Liver Unit, Birmingham, UK; and Clinical Chemistry (Dr. Gray), Children's Hospital, Birmingham, UK.
Address correspondence and reprint requests to Dr Naviaux, Mitochondrial and Metabolic Disease Center, 214 Dickinson St., MC8467, San Diego, CA 92103-2071; e-mail: naviaux{at}ucsd.edu.
Described are six patients with Alpers syndrome from four unrelated families. Affected individuals harbored the following combinations of POLG mutations: 1) A467T/W1020X, 2) W748S-E1143G/G848S, 3) A467T/A467T, and 4) A467T/G848S. Homozygosity for the A467T allele in one patient was associated with a later age at onset. Mitochondrial respiratory chain studies in skeletal muscle were normal in each case. Nine combinations of mutant POLG alleles that cause Alpers syndrome are summarized.
Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the November 8 issue to find the title link for this article.
This article was previously published in electronic format as an Expedited E-Pub on September 21, 2005, at www.neurology.org.
Supported by grants from the UCSD Foundation Christini Fund, the William Wright Family Foundation, and the UCSD Department of Medicine to R.K.N.
Disclosure: The authors report no conflicts of interest.
Received April 13, 2005. Accepted in final form July 22, 2005.
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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|
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|
|
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|
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|
|
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|
|
|
|
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|
|
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|
|
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